Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12.
Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12.
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病毒糖表位的保守拓扑结构为HIV抗体2G12的再利用提供了新的靶点。
DOI：
10.1038/s41598-022-06157-z
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发表时间：
2022-02-16
影响因子：
4.6
通讯作者：
Sasisekharan R
中科院分区：
文献类型：
--
作者：
Miller NL;Subramanian V;Clark T;Raman R;Sasisekharan R
复杂的多糖修饰病毒表面蛋白，并在病毒与宿主的相互作用中发挥关键作用。病毒表面的多聚糖可保护易受攻击的蛋白质表位免受宿主免疫，但也可呈现不同的“糖表位”，这些表位可被宿主抗体作为靶点，例如与gp120上的高甘露糖结合的强大的抗HIV抗体2G12。最近发表的两篇论文表明，2G12与SARS-CoV-2和部分甲型流感H3N2病毒上的高甘露聚糖结合。此前，我们的实验室观察到2G12结合和功能抑制一系列流感病毒，包括H3N2和H1N1谱系。在这篇手稿中，我们将这些数据与结构分析结合在一起，以提供2G12-流感相互作用的扩展图景。此外，基于2G12 N-糖链识别的广泛性和促进糖蛋白寡聚糖化的结构因素，我们假设2G12糖基表位可以根据N-糖链的拓扑结构单独从蛋白质结构来定义。我们开发了一个基于N-多糖位点拓扑结构的描述2G12糖表位的模型，并应用该模型在蛋白质数据库中识别病毒，提出推测的2G12糖表位用于分析、诊断和治疗应用。
Complex glycans decorate viral surface proteins and play a critical role in virus–host interactions. Viral surface glycans shield vulnerable protein epitopes from host immunity yet can also present distinct “glycoepitopes” that can be targeted by host antibodies such as the potent anti-HIV antibody 2G12 that binds high-mannose glycans on gp120. Two recent publications demonstrate 2G12 binding to high mannose glycans on SARS-CoV-2 and select Influenza A (Flu) H3N2 viruses. Previously, our lab observed 2G12 binding and functional inhibition of a range of Flu viruses that include H3N2 and H1N1 lineages. In this manuscript, we present these data alongside structural analyses to offer an expanded picture of 2G12-Flu interactions. Further, based on the remarkable breadth of 2G12 N-glycan recognition and the structural factors promoting glycoprotein oligomannosylation, we hypothesize that 2G12 glycoepitopes can be defined from protein structure alone according to N-glycan site topology. We develop a model describing 2G12 glycoepitopes based on N-glycan site topology, and apply the model to identify viruses within the Protein Data Bank presenting putative 2G12 glycoepitopes for 2G12 repurposing toward analytical, diagnostic, and therapeutic applications.
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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：
32.4
作者：
Falkowska, Emilia;Le, Khoa M.;Ramos, Alejandra;Doores, Katie J.;Lee, Jeong Hyun;Blattner, Claudia;Ramirez, Alejandro;Derking, Ronald;van Gils, Marit J.;Liang, Chi-Hui;Mcbride, Ryan;von Bredow, Benjamin;Shivatare, Sachin S.;Wu, Chung-Yi;Chan-Hui, Po-Ying;Liu, Yan;Feizi, Ten;Zwick, Michael B.;Koff, Wayne C.;Seaman, Michael S.;Swiderek, Kristine;Moore, John P.;Evans, David;Paulson, James C.;Wong, Chi-Huey;Ward, Andrew B.;Wilson, Ian A.;Sanders, Rogier W.;Poignard, Pascal;Burton, Dennis R.
通讯作者：
Burton, Dennis R.
DOI：
10.1126/science.1213256
发表时间：
2011-11-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Pejchal R;Doores KJ;Walker LM;Khayat R;Huang PS;Wang SK;Stanfield RL;Julien JP;Ramos A;Crispin M;Depetris R;Katpally U;Marozsan A;Cupo A;Maloveste S;Liu Y;McBride R;Ito Y;Sanders RW;Ogohara C;Paulson JC;Feizi T;Scanlan CN;Wong CH;Moore JP;Olson WC;Ward AB;Poignard P;Schief WR;Burton DR;Wilson IA
通讯作者：
Wilson IA
影响因子：
5.6
作者：
Liu Y;Pan J;Jenni S;Raymond DD;Caradonna T;Do KT;Schmidt AG;Harrison SC;Grigorieff N
通讯作者：
Grigorieff N
影响因子：
16.6
作者：
Chandramouli S;Ciferri C;Nikitin PA;Caló S;Gerrein R;Balabanis K;Monroe J;Hebner C;Lilja AE;Settembre EC;Carfi A
通讯作者：
Carfi A