7x6o

From Proteopedia

Cryo-EM structure of H1 hemagglutinin from A/Washington/05/2011 in complex with a neutralizing antibody 28-12

Structural highlights

7x6o is a 12 chain structure with sequence from Homo sapiens and Influenza A virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

N0C8E5_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:SAAS00363335]

Publication Abstract from PubMed

Most structurally characterized broadly neutralizing antibodies (bnAbs) against influenza A viruses (IAVs) target the conserved conformational epitopes of hemagglutinin (HA). Here, we report a lineage of naturally occurring human antibodies sharing the same germline gene, V(H)3-48/V(K)1-12. These antibodies broadly neutralize the major circulating strains of IAV in vitro and in vivo mainly by binding a contiguous epitope of H3N2 HA, but a conformational epitope of H1N1 HA, respectively. Our structural and functional studies of antibody 28-12 revealed that the continuous amino acids in helix A, particularly N49(HA2) of H3 HA, are critical to determine the binding feature with 28-12. In contrast, the conformational epitope feature is dependent on the discontinuous segments involving helix A, the fusion peptide, and several HA1 residues within H1N1 HA. We report that this antibody was initially selected by H3 (group 2) viruses and evolved via somatic hypermutation to enhance the reactivity to H3 and acquire cross-neutralization to H1 (group 1) virus. These findings enrich our understanding of different antigenic determinants of heterosubtypic influenza viruses for the recognition of bnAbs and provide a reference for the design of influenza vaccines and more effective antiviral drugs.

Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus.,Sun X, Liu C, Lu X, Ling Z, Yi C, Zhang Z, Li Z, Jin M, Wang W, Tang S, Wang F, Wang F, Wangmo S, Chen S, Li L, Ma L, Zhang Y, Yang Z, Dong X, Qian Z, Ding J, Wang D, Cong Y, Sun B Nat Commun. 2022 May 2;13(1):2378. doi: 10.1038/s41467-022-29950-w. PMID:35501328^[1]

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

References

↑ Sun X, Liu C, Lu X, Ling Z, Yi C, Zhang Z, Li Z, Jin M, Wang W, Tang S, Wang F, Wang F, Wangmo S, Chen S, Li L, Ma L, Zhang Y, Yang Z, Dong X, Qian Z, Ding J, Wang D, Cong Y, Sun B. Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus. Nat Commun. 2022 May 2;13(1):2378. PMID:35501328 doi:10.1038/s41467-022-29950-w