7S8G

Structure of anti-LASV Fab 25.10C with FNQI mutation

7S8G の概要

• エントリーDOI: 10.2210/pdb7s8g/pdb
• 分子名称: 25.10C-FNQI Fab Heavy Chain, 25.10C-FNQI Fab Light Chain (3 entities in total)
• 機能のキーワード: anti-lasv fab, elbow mutation, domain swap, antiviral protein, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95012.23

構造登録者

Hastie, K.M.,Enriquez, A.S. (登録日: 2021-09-17, 公開日: 2022-06-01, 最終更新日: 2024-11-20)

主引用文献

Enriquez, A.S.,Buck, T.K.,Li, H.,Norris, M.J.,Moon-Walker, A.,Zandonatti, M.A.,Harkins, S.S.,Robinson, J.E.,Branco, L.M.,Garry, R.F.,Saphire, E.O.,Hastie, K.M.
Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies.
Cell Rep, 39:110841-110841, 2022

PubMed Abstract: Lassa virus (LASV) is the etiologic agent of Lassa Fever, a hemorrhagic disease that is endemic to West Africa. During LASV infection, LASV glycoprotein (GP) engages with multiple host receptors for cell entry. Neutralizing antibodies against GP are rare and principally target quaternary epitopes displayed only on the metastable, pre-fusion conformation of GP. Currently, the structural features of the neutralizing GPC-A antibody competition group are understudied. Structures of two GPC-A antibodies presented here demonstrate that they bind the side of the pre-fusion GP trimer, bridging the GP1 and GP2 subunits. Complementary biochemical analyses indicate that antibody 25.10C, which is broadly specific, neutralizes by inhibiting binding of the endosomal receptor LAMP1 and also by blocking membrane fusion. The other GPC-A antibody, 36.1F, which is lineage-specific, prevents LAMP1 association only. These data illuminate a site of vulnerability on LASV GP and will guide efforts to elicit broadly reactive therapeutics and vaccines.

PubMed: 35613585
DOI: 10.1016/j.celrep.2022.110841

実験手法

X-RAY DIFFRACTION (2.57 Å)