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Crystal structure of vaccine-elicited receptor-binding site targeting antibody LPAF-a.01 in complex with Hemagglutinin H1 A/California/04/2009
Structural highlights
FunctionC3W5S1_I09A0 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).[SAAS:SAAS013829_004_327643][RuleBase:RU003324] Publication Abstract from PubMedMultidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize a multidonor antibody class (LPAF-a class) targeting the HA head. This class exhibits potent viral entry inhibition against H1N1 A/California/04/2009 (CA09) virus. LPAF-a class antibodies derive from the HV2-70 gene and contain a "Tyr-Gly-Asp"-motif, which occludes the HA-sialic acid binding site as revealed by a co-crystal structure with HA. Both germline-reverted and mature LPAF antibodies potently neutralize CA09 virus and have nanomolar affinities for CA09 HA. Moreover, increased frequencies for LPFA-a class antibodies are observed in humans after a single vaccination. Overall, this work highlights the identification of a multidonor class of head-directed influenza-neutralizing antibodies and delineates the mechanism of their recurrent elicitation in humans. Identification and Structure of a Multidonor Class of Head-Directed Influenza-Neutralizing Antibodies Reveal the Mechanism for Its Recurrent Elicitation.,Cheung CS, Fruehwirth A, Paparoditis PCG, Shen CH, Foglierini M, Joyce MG, Leung K, Piccoli L, Rawi R, Silacci-Fregni C, Tsybovsky Y, Verardi R, Wang L, Wang S, Yang ES, Zhang B, Zhang Y, Chuang GY, Corti D, Mascola JR, Shapiro L, Kwong PD, Lanzavecchia A, Zhou T Cell Rep. 2020 Sep 1;32(9):108088. doi: 10.1016/j.celrep.2020.108088. PMID:32877670[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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