7SGF

Lassa virus glycoprotein construct (Josiah GPC-I53-50A) in complex with LAVA01 antibody

7SGF の概要

• エントリーDOI: 10.2210/pdb7sgf/pdb
• EMDBエントリー: 25107 25108 25109
• 分子名称: GPC-I53-50A, LAVA01 mAb - Heavy Chain, LAVA01 mAb - Light Chain, ... (9 entities in total)
• 機能のキーワード: glycoprotein, lassa, josiah, vaccine design, nanoparticle, protein design, 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: 12
• 化学式量合計: 543990.93

構造登録者

Antanasijevic, A.,Brouwer, P.J.M.,Ward, A.B. (登録日: 2021-10-05, 公開日: 2022-10-12, 最終更新日: 2024-10-23)

主引用文献

Brouwer, P.J.M.,Antanasijevic, A.,Ronk, A.J.,Muller-Krauter, H.,Watanabe, Y.,Claireaux, M.,Perrett, H.R.,Bijl, T.P.L.,Grobben, M.,Umotoy, J.C.,Schriek, A.I.,Burger, J.A.,Tejjani, K.,Lloyd, N.M.,Steijaert, T.H.,van Haaren, M.M.,Sliepen, K.,de Taeye, S.W.,van Gils, M.J.,Crispin, M.,Strecker, T.,Bukreyev, A.,Ward, A.B.,Sanders, R.W.
Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
Cell Host Microbe, 30:1759-, 2022

PubMed Abstract: The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.

PubMed: 36400021
DOI: 10.1016/j.chom.2022.10.018

実験手法

ELECTRON MICROSCOPY (4.41 Å)