Structural highlights
Function
[B2LVD7_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 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][SAAS:SAAS01039073] 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]
Publication Abstract from PubMed
Seasonal influenza virus infections can cause significant morbidity and mortality, but the threat from the emergence of a new pandemic influenza strain might have potentially even more devastating consequences. As such, there is intense interest in isolating and characterizing potent neutralizing antibodies that target the hemagglutinin (HA) viral surface glycoprotein. Here, we use cryo-electron microscopy (cryoEM) to decipher the mechanism of action of a potent HA head-directed monoclonal antibody (mAb) bound to an influenza H7 HA. The epitope of the antibody is not solvent accessible in the compact, prefusion conformation that typifies all HA structures to date. Instead, the antibody binds between HA head protomers to an epitope that must be partly or transiently exposed in the prefusion conformation. The "breathing" of the HA protomers is implied by the exposure of this epitope, which is consistent with metastability of class I fusion proteins. This structure likely therefore represents an early structural intermediate in the viral fusion process. Understanding the extent of transient exposure of conserved neutralizing epitopes also may lead to new opportunities to combat influenza that have not been appreciated previously.
Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains.,Turner HL, Pallesen J, Lang S, Bangaru S, Urata S, Li S, Cottrell CA, Bowman CA, Crowe JE Jr, Wilson IA, Ward AB PLoS Biol. 2019 Feb 4;17(2):e3000139. doi: 10.1371/journal.pbio.3000139., eCollection 2019 Feb. PMID:30716060[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Turner HL, Pallesen J, Lang S, Bangaru S, Urata S, Li S, Cottrell CA, Bowman CA, Crowe JE Jr, Wilson IA, Ward AB. Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains. PLoS Biol. 2019 Feb 4;17(2):e3000139. doi: 10.1371/journal.pbio.3000139., eCollection 2019 Feb. PMID:30716060 doi:http://dx.doi.org/10.1371/journal.pbio.3000139
