Stability and Water Accessibility of the Trimeric Membrane Anchors of the HIV-1 Envelope Spikes.
Stability and Water Accessibility of the Trimeric Membrane Anchors of the HIV-1 Envelope Spikes.
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DOI：
10.1021/jacs.7b09352
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发表时间：
2017-12-27
影响因子：
15
通讯作者：
Chou JJ
中科院分区：
文献类型：
--
作者：
Piai A;Dev J;Fu Q;Chou JJ
HIV-1包膜刺突（Env）是介导病毒进入的I型膜蛋白。最近的研究表明，Env的跨膜结构域（TMD）在脂质双层中形成三聚体，并且TMD的破坏可以显著改变Env的抗原特性。战区导弹防御系统的结构有几个特殊的特点，仍然难以解释。一个是在TM螺旋中间存在精氨酸R696（三聚体中有三个）。此外，TM螺旋的N-和C-末端的一半形成相反性质的三聚体核心（N半为疏水性，C半为亲水性）。在这里，我们确定的膜分区和溶剂的可及性的TMD在双胞，模仿脂质双层。溶剂顺磁弛豫增强分析表明，R696确实位于靠近双层的中心，但令人惊讶的是，可以与水迅速交换，如氢-氘交换测量所示。R696的溶剂可及性可能是由亲水性核介导的，其也显示出快速的水交换。相比之下，N-末端疏水核心显示出极慢的溶剂交换，表明由该区域形成的三聚体非常稳定。我们的数据解释了R696如何被容纳在膜的中间，同时报告了Env TMD三聚体在脂质双层中的总体稳定性。HIV包膜糖蛋白（Env）是病毒体表面上与疫苗设计相关的唯一抗原。最近，确定了HIV-1 Env的三聚体跨膜结构域（TMD）的NMR结构。该结构揭示了一个非常不寻常的特征，即三个保守的组氨酸（每个原聚体一个）位于跨膜螺旋的中间，这表明三个电荷在膜中间的位置是不利的。使用理想的bicelles，溶剂顺磁弛豫增强分析，和氢-氘交换测量的组合，我们提供了直接的证据，有争议的cocinines可以访问水从散装溶剂通过的C-末端亲水性核心的TMD，从而使他们水合，尽管是在中间的脂质双层。我们还发现TMD的N-末端疏水核心形成了一个非常稳定的三聚体，可能是为了维持MPER的未知构象。我们的研究提供了一个解释如何膜包埋的精氨酸是耐受的Env TMD，同时报告的整体稳定性的HIV-1 Env的三聚体膜锚在脂质双层。
HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. Recent studies showed that the transmembrane domain (TMD) of the Env forms a trimer in lipid bilayer and that disruption of the TMD could significantly alter the antigenic properties of the Env. The TMD structure has several peculiar features that remain difficult to explain. One is the presence of an arginine R696 (three in the trimer) in the middle of the TM helix. Additionally, the N- and C-terminal halves of the TM helix form trimeric cores of opposite nature (hydrophobic for the N half and hydrophilic for the C half). Here we determined the membrane partition and solvent accessibility of the TMD in bicelles that mimic a lipid bilayer. Solvent paramagnetic relaxation enhancement analysis showed that the R696 is indeed positioned close to the center of the bilayer, but, surprisingly, can exchange rapidly with water as indicated by hydrogen-deuterium exchange measurements. The solvent accessibility of R696 is likely mediated by the hydrophilic core, which also showed fast water exchange. In contrast, the N-terminal hydrophobic core showed extremely slow solvent exchange, suggesting the trimer formed by this region is extraordinarily stable. Our data explain how R696 is accommodated in the middle of the membrane while reporting the overall stability of the Env TMD trimer in lipid bilayer. The HIV envelope glycoproteins (Env) are the sole antigens on the virion surface relevant for vaccine design. Recently, the NMR structure of the trimeric transmembrane domain (TMD) of the HIV-1 Env was determined. The structure revealed a highly unusual feature that three conserved arginines (one per protomer) are in the middle of the transmembrane helices, suggesting the unfavorable placement of three charges in the middle of the membrane. Using a combination of ideal bicelles, solvent paramagnetic relaxation enhancement analysis, and hydrogen-deuterium exchange measurement, we provide direct evidences that the controversial arginines can access water from the bulk solvent via the C-terminal hydrophilic core of the TMD, thus allowing them to hydrate despite being in the middle of a lipid bilayer. We also found that the N-terminal hydrophobic core of the TMD forms an extremely stable trimer, perhaps for maintaining the yet unknown conformation of the MPER. Our study provides an explanation for how the membrane-embedded arginines are tolerated in the Env TMD while reporting the overall stability of the trimeric membrane anchor of the HIV-1 Env in lipid bilayer.
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影响因子：
15
作者：
Kneller, JM;Lu, M;Bracken, C
通讯作者：
Bracken, C
DOI：
10.1126/science.aaa9804
发表时间：
2015-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen J;Kovacs JM;Peng H;Rits-Volloch S;Lu J;Park D;Zablowsky E;Seaman MS;Chen B
通讯作者：
Chen B
影响因子：
64.8
作者：
Pancera, Marie;Zhou, Tongqing;Druz, Aliaksandr;Georgiev, Ivelin S.;Soto, Cinque;Gorman, Jason;Huang, Jinghe;Acharya, Priyamvada;Chuang, Gwo-Yu;Ofek, Gilad;Stewart-Jones, Guillaume B. E.;Stuckey, Jonathan;Bailer, Robert T.;Joyce, M. Gordon;Louder, Mark K.;Tumba, Nancy;Yang, Yongping;Zhang, Baoshan;Cohen, Myron S.;Haynes, Barton F.;Mascola, John R.;Morris, Lynn;Munro, James B.;Blanchard, Scott C.;Mothes, Walther;Connors, Mark;Kwong, Peter D.
通讯作者：
Kwong, Peter D.
DOI：
10.1111/febs.13954
发表时间：
2017-04
期刊：
The FEBS journal
影响因子：
--
作者：
Chen B;Chou JJ
通讯作者：
Chou JJ
影响因子：
64.8
作者：
Weissenhorn, W;Dessen, A;Wiley, DC
通讯作者：
Wiley, DC