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5c0r

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Revision as of 06:10, 30 September 2015

Crystal Structure of a Generation 3 Influenza Hemagglutinin Stabilized Stem Complexed with the Broadly Neutralizing Antibody C179

Structural highlights

5c0r is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4hlz, 5c0s
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[Q6WG00_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 (By similarity).[SAAS:SAAS00204388]

Publication Abstract from PubMed

The antibody response to influenza is primarily focused on the head region of the hemagglutinin (HA) glycoprotein, which in turn undergoes antigenic drift, thus necessitating annual updates of influenza vaccines. In contrast, the immunogenically subdominant stem region of HA is highly conserved and recognized by antibodies capable of binding multiple HA subtypes. Here we report the structure-based development of an H1 HA stem-only immunogen that confers heterosubtypic protection in mice and ferrets. Six iterative cycles of structure-based design (Gen1-Gen6) yielded successive H1 HA stabilized-stem (HA-SS) immunogens that lack the immunodominant head domain. Antigenic characterization, determination of two HA-SS crystal structures in complex with stem-specific monoclonal antibodies and cryo-electron microscopy analysis of HA-SS on ferritin nanoparticles (H1-SS-np) confirmed the preservation of key structural elements. Vaccination of mice and ferrets with H1-SS-np elicited broadly cross-reactive antibodies that completely protected mice and partially protected ferrets against lethal heterosubtypic H5N1 influenza virus challenge despite the absence of detectable H5N1 neutralizing activity in vitro. Passive transfer of immunoglobulin from H1-SS-np-immunized mice to naive mice conferred protection against H5N1 challenge, indicating that vaccine-elicited HA stem-specific antibodies can protect against diverse group 1 influenza strains.

Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection.,Yassine HM, Boyington JC, McTamney PM, Wei CJ, Kanekiyo M, Kong WP, Gallagher JR, Wang L, Zhang Y, Joyce MG, Lingwood D, Moin SM, Andersen H, Okuno Y, Rao SS, Harris AK, Kwong PD, Mascola JR, Nabel GJ, Graham BS Nat Med. 2015 Aug 24. doi: 10.1038/nm.3927. PMID:26301691^[1]

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

References

↑ Yassine HM, Boyington JC, McTamney PM, Wei CJ, Kanekiyo M, Kong WP, Gallagher JR, Wang L, Zhang Y, Joyce MG, Lingwood D, Moin SM, Andersen H, Okuno Y, Rao SS, Harris AK, Kwong PD, Mascola JR, Nabel GJ, Graham BS. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015 Aug 24. doi: 10.1038/nm.3927. PMID:26301691 doi:http://dx.doi.org/10.1038/nm.3927

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5c0r"

@@ Line 5: / Line 5: @@
 </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hlz|4hlz]], [[5c0s|5c0s]]</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=5c0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c0r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5c0r RCSB], [http://www.ebi.ac.uk/pdbsum/5c0r 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=5c0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c0r OCA], [http://pdbe.org/5c0r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c0r RCSB], [http://www.ebi.ac.uk/pdbsum/5c0r PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 5c0r" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

5c0r

From Proteopedia

Revision as of 06:10, 30 September 2015

Crystal Structure of a Generation 3 Influenza Hemagglutinin Stabilized Stem Complexed with the Broadly Neutralizing Antibody C179

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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