6nhq

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Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin HA2 I45M mutant

Structural highlights

6nhq is a 6 chain structure with sequence from 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 2.5Å
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 human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine.

Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses.,Wu NC, Thompson AJ, Lee JM, Su W, Arlian BM, Xie J, Lerner RA, Yen HL, Bloom JD, Wilson IA Science. 2020 Jun 19;368(6497):1335-1340. doi: 10.1126/science.aaz5143. PMID:32554590^[1]

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

References

↑ Wu NC, Thompson AJ, Lee JM, Su W, Arlian BM, Xie J, Lerner RA, Yen HL, Bloom JD, Wilson IA. Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses. Science. 2020 Jun 19;368(6497):1335-1340. PMID:32554590 doi:10.1126/science.aaz5143