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4nm8

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Crystal structure of broadly neutralizing antibody CR8043 bound to H3 influenza hemagglutinin

Structural highlights

4nm8 is a 12 chain structure with sequence from Homo sapiens and Influenza A virus (A/Hong Kong/1/1968(H3N2)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4.0041Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HEMA_I68A4 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).

Publication Abstract from PubMed

The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.

A common solution to group 2 influenza virus neutralization.,Friesen RH, Lee PS, Stoop EJ, Hoffman RM, Ekiert DC, Bhabha G, Yu W, Juraszek J, Koudstaal W, Jongeneelen M, Korse HJ, Ophorst C, Brinkman-van der Linden EC, Throsby M, Kwakkenbos MJ, Bakker AQ, Beaumont T, Spits H, Kwaks T, Vogels R, Ward AB, Goudsmit J, Wilson IA Proc Natl Acad Sci U S A. 2013 Dec 11. PMID:24335589^[1]

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

References

↑ Friesen RH, Lee PS, Stoop EJ, Hoffman RM, Ekiert DC, Bhabha G, Yu W, Juraszek J, Koudstaal W, Jongeneelen M, Korse HJ, Ophorst C, Brinkman-van der Linden EC, Throsby M, Kwakkenbos MJ, Bakker AQ, Beaumont T, Spits H, Kwaks T, Vogels R, Ward AB, Goudsmit J, Wilson IA. A common solution to group 2 influenza virus neutralization. Proc Natl Acad Sci U S A. 2013 Dec 11. PMID:24335589 doi:http://dx.doi.org/10.1073/pnas.1319058110

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/4nm8"

Categories: Homo sapiens | Large Structures | Lee PS | Wilson IA

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4nm8]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Hong_Kong/1/1968(H3N2)) Influenza A virus (A/Hong Kong/1/1968(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NM8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.0041&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nm8 OCA], [https://pdbe.org/4nm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nm8 RCSB], [https://www.ebi.ac.uk/pdbsum/4nm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nm8 ProSAT]</span></td></tr>
 </table>

4nm8

From Proteopedia

Current revision

Crystal structure of broadly neutralizing antibody CR8043 bound to H3 influenza hemagglutinin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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