8f38

From Proteopedia

Cryo-EM structure of X6 COBRA (H1N1) hemagglutinin bound to CR6261 Fab

Structural highlights

8f38 is a 9 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.64Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HEMA_I00A1 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 either through clathrin-dependent endocytosis or through 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.[HAMAP-Rule:MF_04072]

Publication Abstract from PubMed

Influenza causes significant morbidity and mortality. As an alternative approach to current seasonal vaccines, the computationally optimized broadly reactive antigen (COBRA) platform has been previously applied to hemagglutinin (HA). This approach integrates wild-type HA sequences into a single immunogen to expand the breadth of accessible antibody epitopes. Adding to previous studies of H1, H3, and H5 COBRA HAs, we define the structural features of another H1 subtype COBRA, X6, that incorporates HA sequences from before and after the 2009 H1N1 influenza pandemic. We determined structures of this antigen alone and in complex with COBRA-specific as well as broadly reactive and functional antibodies, analyzing its antigenicity. We found that X6 possesses features representing both historic and recent H1 HA strains, enabling binding to both head- and stem-reactive antibodies. Overall, these data confirm the integrity of broadly reactive antibody epitopes of X6 and contribute to design efforts for a next-generation vaccine.

Structural basis for the broad antigenicity of the computationally optimized influenza hemagglutinin X6.,Nagashima KA, Dzimianski JV, Yang M, Abendroth J, Sautto GA, Ross TM, DuBois RM, Edwards TE, Mousa JJ Structure. 2024 May 24:S0969-2126(24)00178-3. doi: 10.1016/j.str.2024.05.001. PMID:38810648^[1]

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

References

↑ Nagashima KA, Dzimianski JV, Yang M, Abendroth J, Sautto GA, Ross TM, DuBois RM, Edwards TE, Mousa JJ. Structural basis for the broad antigenicity of the computationally optimized influenza hemagglutinin X6. Structure. 2024 May 24:S0969-2126(24)00178-3. PMID:38810648 doi:10.1016/j.str.2024.05.001