Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
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狂犬病病毒糖蛋白三聚体与融合前特异性中和抗体结合的结构。
DOI：
10.1126/sciadv.abp9151
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发表时间：
2022-06-17
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
如果不治疗，狂犬病感染几乎是100%致命的，每年造成5万多人死亡，其中许多是儿童。现有的狂犬病疫苗靶向狂犬病病毒糖蛋白（RABV-G），但产生短暂的免疫应答，这可能是因为该蛋白在生理条件下是异质的。在这里，我们报告了三聚体，融合前RABV-G与RVA 122（一种有效的中和人抗体）复合的3.39 kDa冷冻电镜结构。RVA 122结合RABV-G顶部的四级表位，桥接结构域并稳定融合前状态的RABV-G原体。RABV-G三聚化涉及中心α螺旋和相邻环之间的侧对侧相互作用，而不是中心螺旋之间的接触，以及糖蛋白碱基处融合环之间的相互作用。这些结果为基于融合前构象稳定的RABV-G开发改进的狂犬病疫苗提供了基础。融合环和中和抗体RVA 122使狂犬病病毒糖蛋白稳定在其融合前的三聚体构象。
Rabies infection is nearly 100% lethal if untreated and kills more than 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because the protein is heterogeneous under physiological conditions. Here, we report the 3.39 Å cryo–electron microscopy structure of trimeric, prefusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to a quaternary epitope at the top of RABV-G, bridging domains and stabilizing RABV-G protomers in a prefusion state. RABV-G trimerization involves side-to-side interactions between the central α helix and adjacent loops, rather than contacts between central helices, and interactions among the fusion loops at the glycoprotein base. These results provide a basis from which to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation. Fusion loops and neutralizing antibody RVA122 stabilize rabies virus glycoprotein in its prefusion, trimeric conformation.
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影响因子：
4.6
作者：
Hueffer K;Khatri S;Rideout S;Harris MB;Papke RL;Stokes C;Schulte MK
通讯作者：
Schulte MK
影响因子：
3.7
作者：
Gaudin Y;Ruigrok RW;Tuffereau C;Knossow M;Flamand A
通讯作者：
Flamand A
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
3.8
作者：
Hampson K;Coudeville L;Lembo T;Sambo M;Kieffer A;Attlan M;Barrat J;Blanton JD;Briggs DJ;Cleaveland S;Costa P;Freuling CM;Hiby E;Knopf L;Leanes F;Meslin FX;Metlin A;Miranda ME;Müller T;Nel LH;Recuenco S;Rupprecht CE;Schumacher C;Taylor L;Vigilato MA;Zinsstag J;Dushoff J;Global Alliance for Rabies Control Partners for Rabies Prevention
通讯作者：
Global Alliance for Rabies Control Partners for Rabies Prevention
影响因子：
11.1
作者：
de Melo GD;Sonthonnax F;Lepousez G;Jouvion G;Minola A;Zatta F;Larrous F;Kergoat L;Mazo C;Moigneu C;Aiello R;Salomoni A;Brisebard E;De Benedictis P;Corti D;Bourhy H
通讯作者：
Bourhy H