Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage
Identifieur interne : 000A46 ( Main/Exploration ); précédent : 000A45; suivant : 000A47Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage
Auteurs : Xishan Lu [République populaire de Chine] ; Yi Shi [République populaire de Chine] ; Feng Gao [République populaire de Chine] ; Haixia Xiao [République populaire de Chine] ; Ming Wang [République populaire de Chine] ; Jianxun Qi [République populaire de Chine] ; George F. Gao [République populaire de Chine]Source :
- Journal of Virology [ 0022-538X ] ; 2012.
Abstract
With a new serotype (H17) of hemagglutinin (HA) recently being discovered, there are now 17 serotypes (H1 to H17) of influenza A viruses in total. It is believed that HA is initially expressed as a precursor of HA0 and then cleaved into HA1 and HA2, forming a disulfide bond-linked complex, for its full function. Structural data show that a loop structure exists in the cleavage site between HA1 and HA2, and this flexible loop is crucial for the efficient cleavage of HA0. Here, the crystal structures of H16 (a low-pathogenicity avian influenza virus) in their HA0 form (H16HA0) have been solved at 1.7-Å and 2.0-Å resolutions. To our surprise, an α-helix element in the cleavage site which inserts into the negatively charged cavity with the key residue R329 hidden behind the helix was observed.
Url:
DOI: 10.1128/JVI.01606-12
PubMed: 22993148
PubMed Central: 3497694
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000656
- to stream Pmc, to step Curation: 000656
- to stream Pmc, to step Checkpoint: 000711
- to stream Ncbi, to step Merge: 000812
- to stream Ncbi, to step Curation: 000812
- to stream Ncbi, to step Checkpoint: 000812
- to stream Main, to step Merge: 000A46
- to stream Main, to step Curation: 000A46
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage</title>
<author><name sortKey="Lu, Xishan" sort="Lu, Xishan" uniqKey="Lu X" first="Xishan" last="Lu">Xishan Lu</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, China Agricultural University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name>
<affiliation wicri:level="3"><nlm:aff id="aff3">National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xiao, Haixia" sort="Xiao, Haixia" uniqKey="Xiao H" first="Haixia" last="Xiao">Haixia Xiao</name>
<affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Ming" sort="Wang, Ming" uniqKey="Wang M" first="Ming" last="Wang">Ming Wang</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, China Agricultural University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, China Agricultural University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff5">Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22993148</idno>
<idno type="pmc">3497694</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497694</idno>
<idno type="RBID">PMC:3497694</idno>
<idno type="doi">10.1128/JVI.01606-12</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000656</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000656</idno>
<idno type="wicri:Area/Pmc/Curation">000656</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000656</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000711</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000711</idno>
<idno type="wicri:Area/Ncbi/Merge">000812</idno>
<idno type="wicri:Area/Ncbi/Curation">000812</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000812</idno>
<idno type="wicri:doubleKey">0022-538X:2012:Lu X:insights:into:avian</idno>
<idno type="wicri:Area/Main/Merge">000A46</idno>
<idno type="wicri:Area/Main/Curation">000A46</idno>
<idno type="wicri:Area/Main/Exploration">000A46</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage</title>
<author><name sortKey="Lu, Xishan" sort="Lu, Xishan" uniqKey="Lu X" first="Xishan" last="Lu">Xishan Lu</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, China Agricultural University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name>
<affiliation wicri:level="3"><nlm:aff id="aff3">National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xiao, Haixia" sort="Xiao, Haixia" uniqKey="Xiao H" first="Haixia" last="Xiao">Haixia Xiao</name>
<affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Ming" sort="Wang, Ming" uniqKey="Wang M" first="Ming" last="Wang">Ming Wang</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, China Agricultural University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">College of Veterinary Medicine, China Agricultural University, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, China Agricultural University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff2">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff4">Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea>
<placeName><settlement type="city">Tianjin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff5">Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>With a new serotype (H17) of hemagglutinin (HA) recently being discovered, there are now 17 serotypes (H1 to H17) of influenza A viruses in total. It is believed that HA is initially expressed as a precursor of HA0 and then cleaved into HA1 and HA2, forming a disulfide bond-linked complex, for its full function. Structural data show that a loop structure exists in the cleavage site between HA1 and HA2, and this flexible loop is crucial for the efficient cleavage of HA0. Here, the crystal structures of H16 (a low-pathogenicity avian influenza virus) in their HA0 form (H16HA0) have been solved at 1.7-Å and 2.0-Å resolutions. To our surprise, an α-helix element in the cleavage site which inserts into the negatively charged cavity with the key residue R329 hidden behind the helix was observed. <italic>In vitro</italic>
trypsin cleavage experiments demonstrated inefficient cleavage of H16HA0 under both neutral and low-pH conditions. The results provide new insights into influenza A virus pathogenicity; both the relatively stable α-helix structure in the flexible cleavage loop and inaccessibility of the cleavage site likely contribute to the low pathogenicity of avian influenza A virus. Furthermore, compared to all of the HAs whose structures have been solved, H16 is a good reference for assigning the HA subtypes into two groups on the basis of the three-dimensional structure, which is consistent with the phylogenetic grouping. We conclude that in light of the current H16HA0 structure, the natural α-helix element might provide a new opportunity for influenza virus inhibitor design.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
<settlement><li>Pékin</li>
<li>Tianjin</li>
</settlement>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Lu, Xishan" sort="Lu, Xishan" uniqKey="Lu X" first="Xishan" last="Lu">Xishan Lu</name>
</noRegion>
<name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Lu, Xishan" sort="Lu, Xishan" uniqKey="Lu X" first="Xishan" last="Lu">Xishan Lu</name>
<name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<name sortKey="Shi, Yi" sort="Shi, Yi" uniqKey="Shi Y" first="Yi" last="Shi">Yi Shi</name>
<name sortKey="Wang, Ming" sort="Wang, Ming" uniqKey="Wang M" first="Ming" last="Wang">Ming Wang</name>
<name sortKey="Xiao, Haixia" sort="Xiao, Haixia" uniqKey="Xiao H" first="Haixia" last="Xiao">Haixia Xiao</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A46 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000A46 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= H2N2V1 |flux= Main |étape= Exploration |type= RBID |clé= PMC:3497694 |texte= Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:22993148" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a H2N2V1
This area was generated with Dilib version V0.6.33. |