Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies
Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies
复制标题
狂犬病病毒融合前三聚体糖蛋白与两种保护性抗体复合物的结构
DOI：
10.1101/2022.02.28.482293
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ng W
中科院分区：
文献类型：
--
作者：
Ng W
狂犬病病毒 (RABV) 会引起致命性脑炎，每年导致约 60,000 人死亡。作为唯一的病毒颗粒表面蛋白，狂犬病病毒糖蛋白（RABV-G）介导宿主细胞进入。 RABV-G 的融合前三聚体构象显示出与保护性中和抗体结合的表位，这些表位可以通过疫苗接种诱导或被动施用用于暴露后预防。我们报告了融合前构象的 RABV-G 三聚体的 2.8-Å 结构，与识别不同表位的两种中和和保护性单克隆抗体 17C7 和 1112-1 形成复合物。其中一种抗体是获得许可的预防剂（17C7，Rabishield），我们证明它可以将蛋白质锁定在融合前构象。靶向突变同样可以将 RABV-G 稳定在融合前构象，这是结构引导疫苗设计的关键一步。这些数据揭示了关键治疗靶点的高阶结构以及结合两个关键抗原位点的抗体中和的结构基础，这将有助于改进疫苗和预防性抗体的开发。
Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-Å structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies.
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影响因子：
5.5
作者：
Sloan, Susan E.;Hanlon, Cathleen;Ambrosino, Donna M.
通讯作者：
Ambrosino, Donna M.
影响因子：
56.9
作者：
LENTZ, TL;BURRAGE, TG;TIGNOR, GH
通讯作者：
TIGNOR, GH
一致。
DOI：
10.1097/iae.0000000000001602
发表时间：
2017
期刊：
Retina (Philadelphia, Pa.)
影响因子：
--
作者：
Todorich,Bozho;Thanos,Aristomenis;Yonekawa,Yoshihiro;Thomas,BenjaminJ;Faia,LisaJ;Chang,Emmanuel;Shulman,Julia;Olsen,KarlR;Blair,MichaelP;Shapiro,MichaelP;Ferrone,Philip;Vajzovic,Lejla;Toth,CynthiaA;Lee,ThomasC;Robinson,
通讯作者：
Robinson,
DOI：
10.1073/pnas.80.1.70
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DIETZSCHOLD, B;WUNNER, WH;KOPROWSKI, H
通讯作者：
KOPROWSKI, H
影响因子：
8.8
作者：
Kim EJ;Jacobs MW;Ito-Cole T;Callaway EM
通讯作者：
Callaway EM