Structural highlights
Function
Q1KHJ8_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.[SAAS:SAAS01039674] 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
HA plays a critical role in influenza infection and, thus HA is a potential target for antivirals. Recently, our laboratories have described a novel fusion inhibitor, termed CBS1117, with EC(50) approximately 3 muM against group 1 HA. In this work, we characterize the binding properties of CBS1117 to avian H5 HA by x-ray crystallography, NMR, and mutagenesis. The x-ray structure of the complex shows that the compound binds near the HA fusion peptide, a region that plays a critical role in HA-mediated fusion. NMR studies demonstrate binding of CBS1117 to H5 HA in solution and show extensive hydrophobic contacts between the compound and HA surface. Mutagenesis studies further support the location of the compound binding site proximal to the HA fusion peptide and identify additional amino acids that are important to compound binding. Together, this work gives new insights into the CBS1117 mechanism of action and can be exploited to further optimize this compound and better understand the group specific activity of small-molecule inhibitors of HA-mediated entry.
Structure of avian influenza hemagglutinin in complex with a small molecule entry inhibitor.,Antanasijevic A, Durst MA, Cheng H, Gaisina IN, Perez JT, Manicassamy B, Rong L, Lavie A, Caffrey M Life Sci Alliance. 2020 Jul 1;3(8):e202000724. doi: 10.26508/lsa.202000724. Print , 2020 Aug. PMID:32611549[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Antanasijevic A, Durst MA, Cheng H, Gaisina IN, Perez JT, Manicassamy B, Rong L, Lavie A, Caffrey M. Structure of avian influenza hemagglutinin in complex with a small molecule entry inhibitor. Life Sci Alliance. 2020 Jul 1;3(8):e202000724. PMID:32611549 doi:10.26508/lsa.202000724
