6URM
Crystal structure of vaccine-elicited receptor-binding site targeting antibody LPAF-a.01 in complex with Hemagglutinin H1 A/California/04/2009
Summary for 6URM
| Entry DOI | 10.2210/pdb6urm/pdb |
| Descriptor | Hemagglutinin, The heavy chain of antibody LPAF-a.01, The light chain of antibody LPAF-a.01, ... (9 entities in total) |
| Functional Keywords | influenza, antibody, receptor-binding site, immune system, immune system-viral protein complex, immune system/viral protein |
| Biological source | Influenza A virus More |
| Total number of polymer chains | 6 |
| Total formula weight | 209012.82 |
| Authors | Zhou, T.,Cheung, S.F.,Kwong, P.D. (deposition date: 2019-10-23, release date: 2020-09-16, Last modification date: 2024-11-06) |
| Primary citation | Cheung, C.S.,Fruehwirth, A.,Paparoditis, P.C.G.,Shen, C.H.,Foglierini, M.,Joyce, M.G.,Leung, K.,Piccoli, L.,Rawi, R.,Silacci-Fregni, C.,Tsybovsky, Y.,Verardi, R.,Wang, L.,Wang, S.,Yang, E.S.,Zhang, B.,Zhang, Y.,Chuang, G.Y.,Corti, D.,Mascola, J.R.,Shapiro, L.,Kwong, P.D.,Lanzavecchia, A.,Zhou, T. Identification and Structure of a Multidonor Class of Head-Directed Influenza-Neutralizing Antibodies Reveal the Mechanism for Its Recurrent Elicitation. Cell Rep, 32:108088-108088, 2020 Cited by PubMed Abstract: Multidonor 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. PubMed: 32877670DOI: 10.1016/j.celrep.2020.108088 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.65 Å) |
Structure validation
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