Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops.
Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops.
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DOI：
10.1038/srep07025
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发表时间：
2014-11-14
影响因子：
4.6
通讯作者：
Cheng RH
中科院分区：
文献类型：
--
作者：
Moscoso CG;Xing L;Hui J;Hu J;Kalkhoran MB;Yenigun OM;Sun Y;Paavolainen L;Martin L;Vahlne A;Zambonelli C;Barnett SW;Srivastava IK;Cheng RH
推测HIV-1 Env蛋白gp 120的高变环在Env向受体结合诱导的亚稳态的构象转变中发挥作用。全长Env为基础的免疫原，含有整个V2环的结构分析，显示gp 120亚基之间的更紧密的关联，导致一个更小的三聚体直径比缺乏V2的结构。V2和V3′的一个突出的基底四级位置挑战了以前的报道，这将促进gp 41独立的gp 120-gp 120相互作用，并表明高变环促进了表位封闭的四级机制。V2的缺失导致基底膜近端gp 41表位的显著暴露，与其预测的基底位置一致。本文表征的HIV-1 Env的结构特征为环暴露和表位闭塞的范式转变提供了依据，同时为引发广泛中和抗体所需的表位展示提供了实质性的理论基础，并证实了最近报告中忽略的先前相关文献。
Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3′ that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41 epitopes, consistent with its predicted basal location. The structural features of HIV-1 Env characterized here provide grounds for a paradigm shift in loop exposure and epitope occlusion, while providing substantive rationale for epitope display required for elicitation of broadly neutralizing antibodies, as well as substantiating previous pertinent literature disregarded in recent reports.
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影响因子：
5.5
作者：
Cox, Josephine H.;Ferrari, Maria G.;Earl, Patricia;Lane, James R.;Jagodzinski, Linda L.;Polonis, Victoria R.;Kuta, Ellen G.;Boyer, Jean D.;Ratto-Kim, Silvia;Eller, Leigh-Anne;Doan-Trang Pham;Hart, Lydia;Montefiori, David;Ferrari, Guido;Parrish, Stephanie;Weiner, David B.;Moss, Bernard;Kim, Jerome H.;Birx, Deborah;VanCott, Thomas C.
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VanCott, Thomas C.
影响因子：
64.8
作者：
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通讯作者：
Subramaniam, Sriram
影响因子：
5.4
作者：
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通讯作者：
Swanstrom, Ronald
影响因子：
5.4
作者：
Johnson, WE;Morgan, J;Desrosiers, RC
通讯作者：
Desrosiers, RC
影响因子：
5.4
作者：
Gorny, MK;Stamatatos, L;Zolla-Pazner, S
通讯作者：
Zolla-Pazner, S