Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy
Identifieur interne : 000220 ( Istex/Corpus ); précédent : 000219; suivant : 000221Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy
Auteurs : Christoph Böttcher ; Kai Ludwig ; Andreas Herrmann ; Marin Van Heel ; Holger StarkSource :
- FEBS Letters [ 0014-5793 ] ; 1999.
English descriptors
- Teeft :
- Acidic, Angular approach, Angular reconstitution, Biol, Cell biol, Central cavity, Cold spring harb, Conformation, Conformational, Conformational change, Conformational states, Conformational transitions, Crystallographic structure, Digitised micrographs, Distal domains, Ectodomain, Entire ectodomain, Feb, Fourier shell correlation, Fourier space, Fusion capacity, Fusion peptide, Fusion sequence, Geel zwart, Haemagglutinin, Haemagglutinin trimer, Image processing procedure, Individual trimers, Loop region, Membrane, Micrographs, Projection images, Rosette, Skehel, Subunit, Target membrane, Target membranes, Trimer, Trimeric ectodomain, Viral, Viral membrane, Whole trimer.
Abstract
Abstract: The three-dimensional structures of the complete haemagglutinin (HA) of influenza virus A/Japan/305/57 (H2N2) in its native (neutral pH) and membrane fusion-competent (low pH) form by electron cryo-microscopy at a resolution of 10 Å and 14 Å, respectively, have been determined. In the fusion-competent form the subunits remain closely associated preserving typical overall features of the trimeric ectodomain at neutral pH. Rearrangements of the tertiary structure in the distal and the stem parts are associated with the formation of a central cavity through the entire ectodomain. We suggest that the cavity is essential for relocation of the so-called fusion sequence of HA towards the target membrane.
Url:
DOI: 10.1016/S0014-5793(99)01475-1
Links to Exploration step
ISTEX:2E44183DE2006E8235FC42EB2D04C37014438D4ALe document en format XML
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I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Herrmann, Andreas" sort="Herrmann, Andreas" uniqKey="Herrmann A" first="Andreas" last="Herrmann">Andreas Herrmann</name><affiliation><mods:affiliation>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Van Heel, Marin" sort="Van Heel, Marin" uniqKey="Van Heel M" first="Marin" last="Van Heel">Marin Van Heel</name><affiliation><mods:affiliation>Imperial College of Science, Medicine and Technology, Wolfson Laboratories, Department of Biochemistry, London SW7 2AY, UK</mods:affiliation></affiliation></author><author><name sortKey="Stark, Holger" sort="Stark, Holger" uniqKey="Stark H" first="Holger" last="Stark">Holger Stark</name><affiliation><mods:affiliation>Fritz-Haber-Institut, Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. 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Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Herrmann, Andreas" sort="Herrmann, Andreas" uniqKey="Herrmann A" first="Andreas" last="Herrmann">Andreas Herrmann</name><affiliation><mods:affiliation>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Van Heel, Marin" sort="Van Heel, Marin" uniqKey="Van Heel M" first="Marin" last="Van Heel">Marin Van Heel</name><affiliation><mods:affiliation>Imperial College of Science, Medicine and Technology, Wolfson Laboratories, Department of Biochemistry, London SW7 2AY, UK</mods:affiliation></affiliation></author><author><name sortKey="Stark, Holger" sort="Stark, Holger" uniqKey="Stark H" first="Holger" last="Stark">Holger Stark</name><affiliation><mods:affiliation>Fritz-Haber-Institut, Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Fax: (49)-6421-286 7008</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: stark@imt.uni-marburg.de</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">FEBS Letters</title><title level="j" type="abbrev">FEBS</title><idno type="ISSN">0014-5793</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">463</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="255">255</biblScope><biblScope unit="page" to="259">259</biblScope></imprint><idno type="ISSN">0014-5793</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0014-5793</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acidic</term><term>Angular approach</term><term>Angular reconstitution</term><term>Biol</term><term>Cell biol</term><term>Central cavity</term><term>Cold spring harb</term><term>Conformation</term><term>Conformational</term><term>Conformational change</term><term>Conformational states</term><term>Conformational transitions</term><term>Crystallographic structure</term><term>Digitised micrographs</term><term>Distal domains</term><term>Ectodomain</term><term>Entire ectodomain</term><term>Feb</term><term>Fourier shell correlation</term><term>Fourier space</term><term>Fusion capacity</term><term>Fusion peptide</term><term>Fusion sequence</term><term>Geel zwart</term><term>Haemagglutinin</term><term>Haemagglutinin trimer</term><term>Image processing procedure</term><term>Individual trimers</term><term>Loop region</term><term>Membrane</term><term>Micrographs</term><term>Projection images</term><term>Rosette</term><term>Skehel</term><term>Subunit</term><term>Target membrane</term><term>Target membranes</term><term>Trimer</term><term>Trimeric ectodomain</term><term>Viral</term><term>Viral membrane</term><term>Whole trimer</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The three-dimensional structures of the complete haemagglutinin (HA) of influenza virus A/Japan/305/57 (H2N2) in its native (neutral pH) and membrane fusion-competent (low pH) form by electron cryo-microscopy at a resolution of 10 Å and 14 Å, respectively, have been determined. In the fusion-competent form the subunits remain closely associated preserving typical overall features of the trimeric ectodomain at neutral pH. Rearrangements of the tertiary structure in the distal and the stem parts are associated with the formation of a central cavity through the entire ectodomain. 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Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</json:string></affiliations></json:item><json:item><name>Andreas Herrmann</name><affiliations><json:string>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</json:string></affiliations></json:item><json:item><name>Marin van Heel</name><affiliations><json:string>Imperial College of Science, Medicine and Technology, Wolfson Laboratories, Department of Biochemistry, London SW7 2AY, UK</json:string></affiliations></json:item><json:item><name>Holger Stark</name><affiliations><json:string>Fritz-Haber-Institut, Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin, Germany</json:string><json:string>Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany</json:string><json:string>Corresponding author. Fax: (49)-6421-286 7008</json:string><json:string>E-mail: stark@imt.uni-marburg.de</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Electron microscopy</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Fusion</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Influenza</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Hemagglutinin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Structure</value></json:item></subject><arkIstex>ark:/67375/6H6-PCN76582-4</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: The three-dimensional structures of the complete haemagglutinin (HA) of influenza virus A/Japan/305/57 (H2N2) in its native (neutral pH) and membrane fusion-competent (low pH) form by electron cryo-microscopy at a resolution of 10 Å and 14 Å, respectively, have been determined. In the fusion-competent form the subunits remain closely associated preserving typical overall features of the trimeric ectodomain at neutral pH. Rearrangements of the tertiary structure in the distal and the stem parts are associated with the formation of a central cavity through the entire ectodomain. We suggest that the cavity is essential for relocation of the so-called fusion sequence of HA towards the target membrane.</abstract><qualityIndicators><refBibsNative>true</refBibsNative><abstractWordCount>106</abstractWordCount><abstractCharCount>716</abstractCharCount><keywordCount>5</keywordCount><score>7.245</score><pdfWordCount>3973</pdfWordCount><pdfCharCount>23699</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>5</pdfPageCount><pdfPageSize>595 x 795 pts</pdfPageSize></qualityIndicators><title>Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy</title><pmid><json:string>10606732</json:string></pmid><pii><json:string>S0014-5793(99)01475-1</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>FEBS Letters</title><language><json:string>unknown</json:string></language><publicationDate>1999</publicationDate><issn><json:string>0014-5793</json:string></issn><pii><json:string>S0014-5793(00)X0256-6</json:string></pii><volume>463</volume><issue>3</issue><pages><first>255</first><last>259</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>9-12-99</json:string><json:string>1999</json:string><json:string>2928</json:string></date><geogName></geogName><orgName><json:string>Department of Biochemistry, London SW</json:string><json:string>Sigma Chemical Corporation</json:string><json:string>Alexis Corporation</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Michael Schatz</json:string><json:string>Ralf Schmidt</json:string><json:string>The</json:string><json:string>Kai Ludwigb</json:string><json:string>van Heeld</json:string><json:string>Andreas Herrmannb</json:string></persName><placeName><json:string>Berlin</json:string><json:string>Switzerland</json:string><json:string>Marburg</json:string><json:string>Germany</json:string><json:string>Japan</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>[6,24, 30,31]</json:string><json:string>[4]</json:string><json:string>[32,33]</json:string><json:string>[7,8]</json:string><json:string>[23]</json:string><json:string>[18]</json:string><json:string>[2,3]</json:string><json:string>[6,7,34]</json:string><json:string>[8]</json:string><json:string>[39]</json:string><json:string>[1]</json:string><json:string>[43]</json:string><json:string>[41,42]</json:string><json:string>[16]</json:string><json:string>[13,14]</json:string><json:string>[1,10,11]</json:string><json:string>[31]</json:string><json:string>[5]</json:string><json:string>[15]</json:string><json:string>[6,7]</json:string><json:string>[24,35]</json:string><json:string>[24,37,38]</json:string><json:string>[9]</json:string><json:string>[40]</json:string><json:string>C. Bottcher et al.</json:string><json:string>[19]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-PCN76582-4</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - cell biology</json:string><json:string>2 - biophysics</json:string><json:string>2 - biochemistry & molecular biology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - biochemistry & molecular biology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Cell Biology</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Genetics</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Molecular Biology</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Biochemistry</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Structural Biology</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Biophysics</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - pathologie infectieuse</json:string></inist></categories><publicationDate>1999</publicationDate><copyrightDate>1999</copyrightDate><doi><json:string>10.1016/S0014-5793(99)01475-1</json:string></doi><id>2E44183DE2006E8235FC42EB2D04C37014438D4A</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-PCN76582-4/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-PCN76582-4/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-PCN76582-4/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a">Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©1999 Federation of European Biochemical Societies</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>1999</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Fig. 1: Electron micrographs of influenza haemagglutinin (HA). HA trimer rosettes were isolated from influenza virus (strain A/Japan/305/57 (H2N2)) and embedded in a matrix of vitreous ice containing Phospho-Tungstic-Acid (PTA, 1% (w/v)). A: After incubation for 10 min at 4°C at neutral pH (7.4). B: After incubation for 10 min at 4°C at low pH (4.9) where HA is in a conformation that can trigger fusion of viral and host membranes. Individual trimers of HA are encircled in white.</note><note type="content">Fig. 2: The 3D structure of the haemagglutinin trimer at neutral pH. 3D reconstruction of the ectodomain of the influenza haemagglutinin trimer (A/Japan/305/57 (H2N2)) at neutral pH determined from cryo-electron micrographs (A) in comparison to the X-ray structure (4), low-pass filtered in order to provide a comparable resolution level (B). Small differences between the X-ray and the EM structure are indicated by arrows. The resolution of the EM structure, calculated from 2928 individual trimers, is ∼10 Å as determined by Fourier Shell Correlation. Whereas in the X-ray structure the membrane region was cleaved off by bromelain treatment, this part of the protein was included into the EM reconstruction, but is not resolved due to lack of contrast caused by the neighbourhood of lipids. The viral membrane, which is not shown in the representation, would then be located at the lower end of the haemagglutinin trimer in a distance of 18 Å.</note><note type="content">Fig. 3: The 3D structure of the fusion-competent haemagglutinin trimer. Stereo views of 3D reconstructions determined from cryo-electron micrographs of the trimeric ectodomain of influenza haemagglutinin (A/Japan/305/57 (H2N2)) at neutral pH (A) and at low pH (pH 4.9) (C). The most significant differences of the two conformational states of haemagglutinin are indicated by numbers: (1) a flattening of the top of the distal domains, (2) a torsion of the ectodomain mainly in the part located above the membrane, (3) a refolding of the stem region of the trimer, and (4) the formation of a continuous central cavity through the whole trimer (B, D).</note><note type="content">Fig. 4: Acidification causes distinct alterations in the HA ectodomain. Changes in the ectodomain of influenza haemagglutinin HA (pH 7.4) upon acidification to pH 4.9 are revealed by extracting a slice from each of the reconstructions. The relevant area is indicated by dotted lines in the secondary structure representation of the X-ray data at neutral pH (PDB ID: 2HMG), centre of the figure. The extracted parts of both EM structures were rotated about 40° to visualise differences which occur in the stem region between neutral (left) and low pH (right) conformation. Upon acidification, the absence of the α-helices at the pH 7 position becomes evident.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy</title><author xml:id="author-0000"><persName><forename type="first">Christoph</forename><surname>Böttcher</surname></persName><affiliation>Freie Universität Berlin, Institut für Chemie/Forschungszentrum für Elektronenmikroskopie, Fabeckstr. 36a, D-14195 Berlin, Germany</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Kai</forename><surname>Ludwig</surname></persName><affiliation>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Andreas</forename><surname>Herrmann</surname></persName><affiliation>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Marin</forename><surname>van Heel</surname></persName><affiliation>Imperial College of Science, Medicine and Technology, Wolfson Laboratories, Department of Biochemistry, London SW7 2AY, UK</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Holger</forename><surname>Stark</surname></persName><email>stark@imt.uni-marburg.de</email><affiliation>Fritz-Haber-Institut, Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin, Germany</affiliation><affiliation>Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany</affiliation><affiliation>Corresponding author. Fax: (49)-6421-286 7008</affiliation></author><idno type="istex">2E44183DE2006E8235FC42EB2D04C37014438D4A</idno><idno type="ark">ark:/67375/6H6-PCN76582-4</idno><idno type="DOI">10.1016/S0014-5793(99)01475-1</idno><idno type="PII">S0014-5793(99)01475-1</idno></analytic><monogr><title level="j">FEBS Letters</title><title level="j" type="abbrev">FEBS</title><idno type="pISSN">0014-5793</idno><idno type="PII">S0014-5793(00)X0256-6</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999"></date><biblScope unit="volume">463</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="255">255</biblScope><biblScope unit="page" to="259">259</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: The three-dimensional structures of the complete haemagglutinin (HA) of influenza virus A/Japan/305/57 (H2N2) in its native (neutral pH) and membrane fusion-competent (low pH) form by electron cryo-microscopy at a resolution of 10 Å and 14 Å, respectively, have been determined. In the fusion-competent form the subunits remain closely associated preserving typical overall features of the trimeric ectodomain at neutral pH. Rearrangements of the tertiary structure in the distal and the stem parts are associated with the formation of a central cavity through the entire ectodomain. We suggest that the cavity is essential for relocation of the so-called fusion sequence of HA towards the target membrane.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Electron microscopy</term></item><item><term>Fusion</term></item><item><term>Influenza</term></item><item><term>Hemagglutinin</term></item><item><term>Structure</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999-10-20">Modified</change><change when="1999">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-PCN76582-4/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>FEBS</jid><aid>22909</aid><ce:pii>S0014-5793(99)01475-1</ce:pii><ce:doi>10.1016/S0014-5793(99)01475-1</ce:doi><ce:copyright type="society" year="1999">Federation of European Biochemical Societies</ce:copyright></item-info><head><ce:title>Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy</ce:title><ce:dedication>Edited by Hans-Dieter Klenk</ce:dedication><ce:author-group><ce:author><ce:given-name>Christoph</ce:given-name><ce:surname>Böttcher</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Kai</ce:given-name><ce:surname>Ludwig</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Andreas</ce:given-name><ce:surname>Herrmann</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Marin</ce:given-name><ce:surname>van Heel</ce:surname><ce:cross-ref refid="AFF4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Holger</ce:given-name><ce:surname>Stark</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF5"><ce:sup>e</ce:sup></ce:cross-ref><ce:cross-ref refid="COR1">*</ce:cross-ref><ce:e-address>stark@imt.uni-marburg.de</ce:e-address></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Freie Universität Berlin, Institut für Chemie/Forschungszentrum für Elektronenmikroskopie, Fabeckstr. 36a, D-14195 Berlin, Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Fritz-Haber-Institut, Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin, Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF4"><ce:label>d</ce:label><ce:textfn>Imperial College of Science, Medicine and Technology, Wolfson Laboratories, Department of Biochemistry, London SW7 2AY, UK</ce:textfn></ce:affiliation><ce:affiliation id="AFF5"><ce:label>e</ce:label><ce:textfn>Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>*</ce:label><ce:text>Corresponding author. Fax: (49)-6421-286 7008</ce:text></ce:correspondence></ce:author-group><ce:date-received day="1" month="10" year="1999"></ce:date-received><ce:date-revised day="20" month="10" year="1999"></ce:date-revised><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>The three-dimensional structures of the <ce:italic>complete</ce:italic> haemagglutinin (HA) of influenza virus A/Japan/305/57 (H2N2) in its native (neutral pH) and membrane fusion-competent (low pH) form by electron cryo-microscopy at a resolution of 10 Å and 14 Å, respectively, have been determined. In the fusion-competent form the subunits remain closely associated preserving typical overall features of the trimeric ectodomain at neutral pH. Rearrangements of the tertiary structure in the distal and the stem parts are associated with the formation of a central cavity through the entire ectodomain. We suggest that the cavity is essential for relocation of the so-called fusion sequence of HA towards the target membrane.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Electron microscopy</ce:text></ce:keyword><ce:keyword><ce:text>Fusion</ce:text></ce:keyword><ce:keyword><ce:text>Influenza</ce:text></ce:keyword><ce:keyword><ce:text>Hemagglutinin</ce:text></ce:keyword><ce:keyword><ce:text>Structure</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Structure of influenza haemagglutinin at neutral and at fusogenic pH by electron cryo-microscopy</title></titleInfo><name type="personal"><namePart type="given">Christoph</namePart><namePart type="family">Böttcher</namePart><affiliation>Freie Universität Berlin, Institut für Chemie/Forschungszentrum für Elektronenmikroskopie, Fabeckstr. 36a, D-14195 Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kai</namePart><namePart type="family">Ludwig</namePart><affiliation>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andreas</namePart><namePart type="family">Herrmann</namePart><affiliation>Humboldt-Universität zu Berlin, Math.-Nat. Fak. I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marin</namePart><namePart type="family">van Heel</namePart><affiliation>Imperial College of Science, Medicine and Technology, Wolfson Laboratories, Department of Biochemistry, London SW7 2AY, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Holger</namePart><namePart type="family">Stark</namePart><affiliation>Fritz-Haber-Institut, Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin, Germany</affiliation><affiliation>Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany</affiliation><affiliation>Corresponding author. Fax: (49)-6421-286 7008</affiliation><affiliation>E-mail: stark@imt.uni-marburg.de</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1999</dateIssued><dateModified encoding="w3cdtf">1999-10-20</dateModified><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: The three-dimensional structures of the complete haemagglutinin (HA) of influenza virus A/Japan/305/57 (H2N2) in its native (neutral pH) and membrane fusion-competent (low pH) form by electron cryo-microscopy at a resolution of 10 Å and 14 Å, respectively, have been determined. In the fusion-competent form the subunits remain closely associated preserving typical overall features of the trimeric ectodomain at neutral pH. Rearrangements of the tertiary structure in the distal and the stem parts are associated with the formation of a central cavity through the entire ectodomain. We suggest that the cavity is essential for relocation of the so-called fusion sequence of HA towards the target membrane.</abstract><note type="content">Fig. 1: Electron micrographs of influenza haemagglutinin (HA). HA trimer rosettes were isolated from influenza virus (strain A/Japan/305/57 (H2N2)) and embedded in a matrix of vitreous ice containing Phospho-Tungstic-Acid (PTA, 1% (w/v)). A: After incubation for 10 min at 4°C at neutral pH (7.4). B: After incubation for 10 min at 4°C at low pH (4.9) where HA is in a conformation that can trigger fusion of viral and host membranes. Individual trimers of HA are encircled in white.</note><note type="content">Fig. 2: The 3D structure of the haemagglutinin trimer at neutral pH. 3D reconstruction of the ectodomain of the influenza haemagglutinin trimer (A/Japan/305/57 (H2N2)) at neutral pH determined from cryo-electron micrographs (A) in comparison to the X-ray structure (4), low-pass filtered in order to provide a comparable resolution level (B). Small differences between the X-ray and the EM structure are indicated by arrows. The resolution of the EM structure, calculated from 2928 individual trimers, is ∼10 Å as determined by Fourier Shell Correlation. Whereas in the X-ray structure the membrane region was cleaved off by bromelain treatment, this part of the protein was included into the EM reconstruction, but is not resolved due to lack of contrast caused by the neighbourhood of lipids. The viral membrane, which is not shown in the representation, would then be located at the lower end of the haemagglutinin trimer in a distance of 18 Å.</note><note type="content">Fig. 3: The 3D structure of the fusion-competent haemagglutinin trimer. Stereo views of 3D reconstructions determined from cryo-electron micrographs of the trimeric ectodomain of influenza haemagglutinin (A/Japan/305/57 (H2N2)) at neutral pH (A) and at low pH (pH 4.9) (C). The most significant differences of the two conformational states of haemagglutinin are indicated by numbers: (1) a flattening of the top of the distal domains, (2) a torsion of the ectodomain mainly in the part located above the membrane, (3) a refolding of the stem region of the trimer, and (4) the formation of a continuous central cavity through the whole trimer (B, D).</note><note type="content">Fig. 4: Acidification causes distinct alterations in the HA ectodomain. Changes in the ectodomain of influenza haemagglutinin HA (pH 7.4) upon acidification to pH 4.9 are revealed by extracting a slice from each of the reconstructions. The relevant area is indicated by dotted lines in the secondary structure representation of the X-ray data at neutral pH (PDB ID: 2HMG), centre of the figure. The extracted parts of both EM structures were rotated about 40° to visualise differences which occur in the stem region between neutral (left) and low pH (right) conformation. Upon acidification, the absence of the α-helices at the pH 7 position becomes evident.</note><subject><genre>Keywords</genre><topic>Electron microscopy</topic><topic>Fusion</topic><topic>Influenza</topic><topic>Hemagglutinin</topic><topic>Structure</topic></subject><relatedItem type="host"><titleInfo><title>FEBS Letters</title></titleInfo><titleInfo type="abbreviated"><title>FEBS</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1999</dateIssued></originInfo><identifier type="ISSN">0014-5793</identifier><identifier type="PII">S0014-5793(00)X0256-6</identifier><part><date>1999</date><detail type="volume"><number>463</number><caption>vol.</caption></detail><detail type="issue"><number>3</number><caption>no.</caption></detail><extent unit="issue-pages"><start>199</start><end>390</end></extent><extent unit="pages"><start>255</start><end>259</end></extent></part></relatedItem><identifier type="istex">2E44183DE2006E8235FC42EB2D04C37014438D4A</identifier><identifier type="ark">ark:/67375/6H6-PCN76582-4</identifier><identifier type="DOI">10.1016/S0014-5793(99)01475-1</identifier><identifier type="PII">S0014-5793(99)01475-1</identifier><accessCondition type="use and reproduction" contentType="copyright">©1999 Federation of European Biochemical Societies</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Federation of European Biochemical Societies, ©1999</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-PCN76582-4/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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