8gav | pdb_00008gav
Structure of human NDS.3 Fab in complex with influenza virus neuraminidase from A/Darwin/09/2021 (H3N2)
Structural highlights
FunctionA0A5B9C3Z7_9INFA Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.[HAMAP-Rule:MF_04071] Publication Abstract from PubMedContinuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the NA antigenic landscape still remains incomplete. Here, we describe NA-specific human antibodies that target the underside of the NA globular head domain, inhibit viral propagation of a wide range of human H3N2, swine-origin variant H3N2, and H2N2 viruses, and confer both pre- and post-exposure protection against lethal H3N2 infection in mice. Cryo-EM structures of two such antibodies in complex with NA reveal non-overlapping epitopes covering the underside of the NA head. These sites are highly conserved among N2 NAs yet inaccessible unless the NA head tilts or dissociates. Our findings help guide the development of effective countermeasures against ever-changing influenza viruses by identifying hidden conserved sites of vulnerability on the NA underside. Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase.,Lederhofer J, Tsybovsky Y, Nguyen L, Raab JE, Creanga A, Stephens T, Gillespie RA, Syeda HZ, Fisher BE, Skertic M, Yap C, Schaub AJ, Rawi R, Kwong PD, Graham BS, McDermott AB, Andrews SF, King NP, Kanekiyo M Immunity. 2024 Mar 12;57(3):574-586.e7. doi: 10.1016/j.immuni.2024.02.003. Epub , 2024 Mar 1. PMID:38430907[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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