6P91

Structure of Lassa virus glycoprotein bound to Fab 18.5C

6P91 の概要

• エントリーDOI: 10.2210/pdb6p91/pdb
• 分子名称: Pre-glycoprotein polyprotein GP complex, Fab 18.5C Antibody heavy chain, Fab 18.5C Antibody light chain, ... (9 entities in total)
• 機能のキーワード: lassa virus, glycoprotein, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Lassa mammarenavirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 104820.01

構造登録者

Saphire, E.O.,Hastie, K.M. (登録日: 2019-06-09, 公開日: 2019-08-21, 最終更新日: 2024-11-20)

主引用文献

Hastie, K.M.,Cross, R.W.,Harkins, S.S.,Zandonatti, M.A.,Koval, A.P.,Heinrich, M.L.,Rowland, M.M.,Robinson, J.E.,Geisbert, T.W.,Garry, R.F.,Branco, L.M.,Saphire, E.O.
Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization.
Cell, 178:1004-1015.e14, 2019

PubMed Abstract: 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.

PubMed: 31398326
DOI: 10.1016/j.cell.2019.07.020

実験手法

X-RAY DIFFRACTION (4 Å)