6p91

Structure of Lassa virus glycoprotein bound to Fab 18.5C

spinqualitylabelsall models 6p91, resolution 4.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6p91 is a 4 chain structure with sequence from Human and Lassa mammarenavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, FUC, MAN, NAG Gene: GP, GPC (Lassa mammarenavirus) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [Q6GWS0_9VIRU] Glycoprotein G1: interacts with the host receptor.[HAMAP-Rule:MF_04084] Glycoprotein G2: class I viral fusion protein that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversible conformational changes induced upon acidification in the endosome.[HAMAP-Rule:MF_04084] Stable signal peptide (SSP): cleaved and functions as a signal peptide. In addition, it is also retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational maturation cleavage of GP1 and GP2, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.[HAMAP-Rule:MF_04084] Publication Abstract from PubMed Lassa virus (LASV) causes hemorrhagic fever and is endemic in West Africa. Protective antibody responses primarily target the LASV surface glycoprotein (GPC), and GPC-B competition group antibodies often show potent neutralizing activity in humans. However, which features confer potent and broadly neutralizing antibody responses is unclear. Here, we compared three crystal structures of LASV GPC complexed with GPC-B antibodies of varying neutralization potency. Each GPC-B antibody recognized an overlapping epitope involved in binding of two adjacent GPC monomers and preserved the prefusion trimeric conformation. Differences among GPC-antibody interactions highlighted specific residues that enhance neutralization. Using structure-guided amino acid substitutions, we increased the neutralization potency and breadth of these antibodies to include all major LASV lineages. The ability to define antibody residues that allow potent and broad neutralizing activity, together with findings from analyses of inferred germline precursors, is critical to develop potent therapeutics and for vaccine design and assessment. Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization.,Hastie KM, Cross RW, Harkins SS, Zandonatti MA, Koval AP, Heinrich ML, Rowland MM, Robinson JE, Geisbert TW, Garry RF, Branco LM, Saphire EO Cell. 2019 Aug 8;178(4):1004-1015.e14. doi: 10.1016/j.cell.2019.07.020. PMID:31398326 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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