8EJD

Structure of lineage IV Lassa virus glycoprotein complex (strain Josiah)

8EJD の概要

• エントリーDOI: 10.2210/pdb8ejd/pdb
• EMDBエントリー: 28178
• 分子名称: Glycoprotein G1, Glycoprotein G2, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: glycoprotein complex, lassa mammarenavirus, lasv, gpc, immune system, viral fusion protein, lassa virus, lineage iv, josiah, viral protein
• 由来する生物種: Lassa mammarenavirus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 238706.31

構造登録者

Perrett, H.R.,Ward, A.B. (登録日: 2022-09-16, 公開日: 2023-06-07, 最終更新日: 2024-11-06)

主引用文献

Perrett, H.R.,Brouwer, P.J.M.,Hurtado, J.,Newby, M.L.,Liu, L.,Muller-Krauter, H.,Muller Aguirre, S.,Burger, J.A.,Bouhuijs, J.H.,Gibson, G.,Messmer, T.,Schieffelin, J.S.,Antanasijevic, A.,Boons, G.J.,Strecker, T.,Crispin, M.,Sanders, R.W.,Briney, B.,Ward, A.B.
Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies.
Cell Rep, 42:112524-112524, 2023

PubMed Abstract: Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.

PubMed: 37209096
DOI: 10.1016/j.celrep.2023.112524

実験手法

ELECTRON MICROSCOPY (3.8 Å)