7UDS

Structure of lineage I (Pinneo) Lassa virus glycoprotein bound to Fab 25.10C

7UDS の概要

• エントリーDOI: 10.2210/pdb7uds/pdb
• EMDBエントリー: 26458
• 分子名称: 25.10C Fab Heavy Chain, 25.10C Fab Light Chain, Glycoprotein G1, ... (8 entities in total)
• 機能のキーワード: viral glycoprotein, antibody fab fragment, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 308840.31

構造登録者

Buck, T.K.,Enriquez, A.E.,Hastie, K.M. (登録日: 2022-03-20, 公開日: 2022-06-15, 最終更新日: 2024-10-23)

主引用文献

Buck, T.K.,Enriquez, A.S.,Schendel, S.L.,Zandonatti, M.A.,Harkins, S.S.,Li, H.,Moon-Walker, A.,Robinson, J.E.,Branco, L.M.,Garry, R.F.,Saphire, E.O.,Hastie, K.M.
Neutralizing Antibodies against Lassa Virus Lineage I.
Mbio, 13:e0127822-e0127822, 2022

PubMed Abstract: Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is particularly resistant to antibody neutralization. Lineage I LASV evades neutralization by half of known antibodies in the GPC-A antibody competition group and all but one of the antibodies in the GPC-B competition group. Here, we solve two cryo-electron microscopy (cryo-EM) structures of LI GP in complex with a GPC-A and a GPC-B antibody. We used complementary structural and biochemical techniques to identify single-amino-acid substitutions in LI that are responsible for immune evasion by each antibody group. Further, we show that LI infection is more dependent on the endosomal receptor lysosome-associated membrane protein 1 (LAMP1) for viral entry relative to LIV. In the absence of LAMP1, LI requires a more acidic fusion pH to initiate membrane fusion with the host cell relative to LIV. No vaccine or therapeutics are approved to prevent LASV infection or treat LF. All vaccine platforms currently under development present only the LIV GP sequence. However, our data suggest that the high genetic diversity of LASV may be problematic for designing both a broadly reactive immunogen and therapeutic. Here, we examine antibodies that are highly potent against LIV yet are ineffective against LI. By pinpointing LI mutations responsible for this decrease in antibody efficacy, we suggest that future vaccine platforms may need to incorporate specific LI-like mutations in order to generate a broadly neutralizing antibody response against all LASV lineages.

PubMed: 35730904
DOI: 10.1128/mbio.01278-22

実験手法

ELECTRON MICROSCOPY (3.1 Å)