5gjs

From Proteopedia

Crystal structure of H1 hemagglutinin from A/California/04/2009 in complex with a neutralizing antibody 3E1

Structural highlights

5gjs is a 4 chain structure with sequence from Homo sapiens and Influenza A virus (A/California/04/2009(H1N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

C3W5S1_I09A0 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:SAAS013829_004_327643][RuleBase:RU003324]

Publication Abstract from PubMed

As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion. The crystal structures of 3E1 Fab in complex with HA of two H1N1 strains reveal that 3E1, with both heavy and light chains, binds to a conserved epitope of the HA stem region, comprising parts of the fusion peptide, the F subdomain and the outermost beta-strand preceding helix A. Altogether, these data suggest the potential of 3E1 as a therapeutic drug against H1 and H5 subtype viruses.

Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses.,Wang W, Sun X, Li Y, Su J, Ling Z, Zhang T, Wang F, Zhang H, Chen H, Ding J, Sun B Nat Commun. 2016 Dec 2;7:13577. doi: 10.1038/ncomms13577. PMID:27910950^[1]

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

References

↑ Wang W, Sun X, Li Y, Su J, Ling Z, Zhang T, Wang F, Zhang H, Chen H, Ding J, Sun B. Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses. Nat Commun. 2016 Dec 2;7:13577. doi: 10.1038/ncomms13577. PMID:27910950 doi:http://dx.doi.org/10.1038/ncomms13577