Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack.
Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack.
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动态HIV-1尖峰运动为其膜结合的三脚架对抗体攻击创造了脆弱性。
DOI：
10.1038/s41467-022-34008-y
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发表时间：
2022-10-27
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
Vaccines targeting HIV-1’s gp160 spike protein are stymied by high viral mutation rates and structural chicanery. gp160’s membrane-proximal external region (MPER) is the target of naturally arising broadly neutralizing antibodies (bnAbs), yet MPER-based vaccines fail to generate bnAbs. Here, nanodisc-embedded spike protein was investigated by cryo-electron microscopy and molecular-dynamics simulations, revealing spontaneous ectodomain tilting that creates vulnerability for HIV-1. While each MPER protomer radiates centrally towards the three-fold axis contributing to a membrane-associated tripod structure that is occluded in the upright spike, tilting provides access to the opposing MPER. Structures of spike proteins with bound 4E10 bnAb Fabs reveal that the antibody binds exposed MPER, thereby altering MPER dynamics, modifying average ectodomain tilt, and imposing strain on the viral membrane and the spike’s transmembrane segments, resulting in the abrogation of membrane fusion and informing future vaccine development. The membrane-proximal external region of HIV-1 spike protein is a broadly neutralizing antibody target. Here, cryo-electron microscopy and molecular dynamics reveal spontaneous ectodomain tilting, a vulnerability exploitable for vaccine design.
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Aldrithiol-2 灭活病毒颗粒上 HIV-1 包膜三聚体的亚纳米结构
影响因子：
16.8
作者：
Li Z;Li W;Lu M;Bess J Jr;Chao CW;Gorman J;Terry DS;Zhang B;Zhou T;Blanchard SC;Kwong PD;Lifson JD;Mothes W;Liu J
通讯作者：
Liu J
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1073/pnas.1807259115
发表时间：
2018-09-18
影响因子：
11.1
作者：
Fu, Qingshan;Shaik, Md Munan;Chou, James J.
通讯作者：
Chou, James J.
影响因子：
64.5
作者：
Bonsignori M;Zhou T;Sheng Z;Chen L;Gao F;Joyce MG;Ozorowski G;Chuang GY;Schramm CA;Wiehe K;Alam SM;Bradley T;Gladden MA;Hwang KK;Iyengar S;Kumar A;Lu X;Luo K;Mangiapani MC;Parks RJ;Song H;Acharya P;Bailer RT;Cao A;Druz A;Georgiev IS;Kwon YD;Louder MK;Zhang B;Zheng A;Hill BJ;Kong R;Soto C;NISC Comparative Sequencing Program;Mullikin JC;Douek DC;Montefiori DC;Moody MA;Shaw GM;Hahn BH;Kelsoe G;Hraber PT;Korber BT;Boyd SD;Fire AZ;Kepler TB;Shapiro L;Ward AB;Mascola JR;Liao HX;Kwong PD;Haynes BF
通讯作者：
Haynes BF
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH