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4f23

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Revision as of 11:34, 4 August 2016

Influenza A virus hemagglutinin H16 HA0 structure with an alpha-helix conformation in the cleavage site: a potential drug target

Structural highlights

4f23 is a 3 chain structure with sequence from Influenza a virus (a/black-headed gull/sweden/2/99(h16n3)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	HA (Influenza A virus (A/black-headed gull/Sweden/2/99(H16N3)))
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[Q5DL24_9INFA] Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[RuleBase:RU003324][SAAS:SAAS00145386]

Publication Abstract from PubMed

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-A and 2.0-A resolutions. To our surprise, an alpha-helix element in the cleavage site which inserts into the negatively charged cavity with the key residue R329 hidden behind the helix was observed. In vitro 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 alpha-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 alpha-helix element might provide a new opportunity for influenza virus inhibitor design.

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.,Lu X, Shi Y, Gao F, Xiao H, Wang M, Qi J, Gao GF J Virol. 2012 Dec;86(23):12861-70. doi: 10.1128/JVI.01606-12. Epub 2012 Sep 19. PMID:22993148^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lu X, Shi Y, Gao F, Xiao H, Wang M, Qi J, Gao GF. 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. J Virol. 2012 Dec;86(23):12861-70. doi: 10.1128/JVI.01606-12. Epub 2012 Sep 19. PMID:22993148 doi:http://dx.doi.org/10.1128/JVI.01606-12

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4f23"

@@ Line 1: / Line 1: @@
 ==Influenza A virus hemagglutinin H16 HA0 structure with an alpha-helix conformation in the cleavage site: a potential drug target==
 <StructureSection load='4f23' size='340' side='right' caption='[[4f23]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=304362 Influenza A virus (A/black-headed gull/Sweden/2/99(H16N3))])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f23 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f23 RCSB], [http://www.ebi.ac.uk/pdbsum/4f23 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f23 OCA], [http://pdbe.org/4f23 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f23 RCSB], [http://www.ebi.ac.uk/pdbsum/4f23 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f23 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4f23" style="background-color:#fffaf0;"></div>
 ==See Also==

4f23

From Proteopedia

Revision as of 11:34, 4 August 2016

Influenza A virus hemagglutinin H16 HA0 structure with an alpha-helix conformation in the cleavage site: a potential drug target

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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