A trimerizing GxxxG motif is uniquely inserted in the severe acute respiratory syndrome (SARS) coronavirus spike protein transmembrane domain.
Identifieur interne : 002091 ( PubMed/Corpus ); précédent : 002090; suivant : 002092A trimerizing GxxxG motif is uniquely inserted in the severe acute respiratory syndrome (SARS) coronavirus spike protein transmembrane domain.
Auteurs : Eyal Arbely ; Zvi Granot ; Itamar Kass ; Joseph Orly ; Isaiah T. ArkinSource :
- Biochemistry [ 0006-2960 ] ; 2006.
English descriptors
- KwdEn :
- Amino Acid Motifs, Amino Acid Sequence, Bacteria (metabolism), Cell Membrane (metabolism), Chloramphenicol O-Acetyltransferase (metabolism), Genetic Complementation Test, Glycine (chemistry), Humans, Membrane Glycoproteins (chemistry), Models, Molecular, Molecular Sequence Data, Protein Structure, Quaternary, Protein Structure, Tertiary, SARS Virus (chemistry), Sequence Alignment, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry).
- MESH :
- chemical , chemistry : Glycine, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Chloramphenicol O-Acetyltransferase.
- chemistry : SARS Virus.
- metabolism : Bacteria, Cell Membrane.
- Amino Acid Motifs, Amino Acid Sequence, Genetic Complementation Test, Humans, Models, Molecular, Molecular Sequence Data, Protein Structure, Quaternary, Protein Structure, Tertiary, Sequence Alignment, Spike Glycoprotein, Coronavirus.
Abstract
In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are unique to its proteins and not present in any other family member. We identified an insertion of two glycine residues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which is not found in any other coronavirus. This surprising finding raises an "oligomerization riddle": the GxxxG motif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an in vivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization is driven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization of the entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-length protein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike protein TMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure, the glycine residues of the GxxxG motif are facing each other, enhancing helix-helix interactions by allowing for the close positioning of the helices. This unique orientation of the glycine residues also stabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipid bilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiate other oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimeric bundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxG motif on this feature is discussed.
DOI: 10.1021/bi060953v
PubMed: 16981695
Links to Exploration step
pubmed:16981695Le document en format XML
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Safra Campus, Givat-Ram, Jerusalem 91904, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Granot, Zvi" sort="Granot, Zvi" uniqKey="Granot Z" first="Zvi" last="Granot">Zvi Granot</name></author><author><name sortKey="Kass, Itamar" sort="Kass, Itamar" uniqKey="Kass I" first="Itamar" last="Kass">Itamar Kass</name></author><author><name sortKey="Orly, Joseph" sort="Orly, Joseph" uniqKey="Orly J" first="Joseph" last="Orly">Joseph Orly</name></author><author><name sortKey="Arkin, Isaiah T" sort="Arkin, Isaiah T" uniqKey="Arkin I" first="Isaiah T" last="Arkin">Isaiah T. Arkin</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="RBID">pubmed:16981695</idno><idno type="pmid">16981695</idno><idno type="doi">10.1021/bi060953v</idno><idno type="wicri:Area/PubMed/Corpus">002091</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002091</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A trimerizing GxxxG motif is uniquely inserted in the severe acute respiratory syndrome (SARS) coronavirus spike protein transmembrane domain.</title><author><name sortKey="Arbely, Eyal" sort="Arbely, Eyal" uniqKey="Arbely E" first="Eyal" last="Arbely">Eyal Arbely</name><affiliation><nlm:affiliation>The Alexander Silberman Institute of Life Sciences, Department of Biological Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat-Ram, Jerusalem 91904, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Granot, Zvi" sort="Granot, Zvi" uniqKey="Granot Z" first="Zvi" last="Granot">Zvi Granot</name></author><author><name sortKey="Kass, Itamar" sort="Kass, Itamar" uniqKey="Kass I" first="Itamar" last="Kass">Itamar Kass</name></author><author><name sortKey="Orly, Joseph" sort="Orly, Joseph" uniqKey="Orly J" first="Joseph" last="Orly">Joseph Orly</name></author><author><name sortKey="Arkin, Isaiah T" sort="Arkin, Isaiah T" uniqKey="Arkin I" first="Isaiah T" last="Arkin">Isaiah T. Arkin</name></author></analytic><series><title level="j">Biochemistry</title><idno type="ISSN">0006-2960</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Bacteria (metabolism)</term><term>Cell Membrane (metabolism)</term><term>Chloramphenicol O-Acetyltransferase (metabolism)</term><term>Genetic Complementation Test</term><term>Glycine (chemistry)</term><term>Humans</term><term>Membrane Glycoproteins (chemistry)</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Structure, Quaternary</term><term>Protein Structure, Tertiary</term><term>SARS Virus (chemistry)</term><term>Sequence Alignment</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (chemistry)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Glycine</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Chloramphenicol O-Acetyltransferase</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Bacteria</term><term>Cell Membrane</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Genetic Complementation Test</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Structure, Quaternary</term><term>Protein Structure, Tertiary</term><term>Sequence Alignment</term><term>Spike Glycoprotein, Coronavirus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are unique to its proteins and not present in any other family member. We identified an insertion of two glycine residues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which is not found in any other coronavirus. This surprising finding raises an "oligomerization riddle": the GxxxG motif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an in vivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization is driven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization of the entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-length protein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike protein TMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure, the glycine residues of the GxxxG motif are facing each other, enhancing helix-helix interactions by allowing for the close positioning of the helices. This unique orientation of the glycine residues also stabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipid bilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiate other oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimeric bundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxG motif on this feature is discussed.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16981695</PMID><DateCompleted><Year>2006</Year><Month>11</Month><Day>08</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0006-2960</ISSN><JournalIssue CitedMedium="Print"><Volume>45</Volume><Issue>38</Issue><PubDate><Year>2006</Year><Month>Sep</Month><Day>26</Day></PubDate></JournalIssue><Title>Biochemistry</Title><ISOAbbreviation>Biochemistry</ISOAbbreviation></Journal><ArticleTitle>A trimerizing GxxxG motif is uniquely inserted in the severe acute respiratory syndrome (SARS) coronavirus spike protein transmembrane domain.</ArticleTitle><Pagination><MedlinePgn>11349-56</MedlinePgn></Pagination><Abstract><AbstractText>In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are unique to its proteins and not present in any other family member. We identified an insertion of two glycine residues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which is not found in any other coronavirus. This surprising finding raises an "oligomerization riddle": the GxxxG motif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an in vivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization is driven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization of the entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-length protein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike protein TMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure, the glycine residues of the GxxxG motif are facing each other, enhancing helix-helix interactions by allowing for the close positioning of the helices. This unique orientation of the glycine residues also stabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipid bilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiate other oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimeric bundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxG motif on this feature is discussed.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Arbely</LastName><ForeName>Eyal</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>The Alexander Silberman Institute of Life Sciences, Department of Biological Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat-Ram, Jerusalem 91904, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Granot</LastName><ForeName>Zvi</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Kass</LastName><ForeName>Itamar</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Orly</LastName><ForeName>Joseph</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Arkin</LastName><ForeName>Isaiah T</ForeName><Initials>IT</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Biochemistry</MedlineTA><NlmUniqueID>0370623</NlmUniqueID><ISSNLinking>0006-2960</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008562">Membrane Glycoproteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014759">Viral Envelope Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C578557">spike glycoprotein, SARS-CoV</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.1.28</RegistryNumber><NameOfSubstance UI="D015500">Chloramphenicol O-Acetyltransferase</NameOfSubstance></Chemical><Chemical><RegistryNumber>TE7660XO1C</RegistryNumber><NameOfSubstance UI="D005998">Glycine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D020816" MajorTopicYN="N">Amino Acid Motifs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001419" MajorTopicYN="N">Bacteria</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002462" MajorTopicYN="N">Cell Membrane</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015500" MajorTopicYN="N">Chloramphenicol O-Acetyltransferase</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005816" MajorTopicYN="N">Genetic Complementation Test</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005998" MajorTopicYN="N">Glycine</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008562" MajorTopicYN="N">Membrane Glycoproteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020836" MajorTopicYN="N">Protein Structure, Quaternary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017434" MajorTopicYN="N">Protein Structure, Tertiary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016415" MajorTopicYN="N">Sequence Alignment</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014759" MajorTopicYN="N">Viral Envelope Proteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>9</Month><Day>20</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>11</Month><Day>10</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>9</Month><Day>20</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">16981695</ArticleId><ArticleId IdType="doi">10.1021/bi060953v</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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