Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion.
Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion.
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DOI：
10.1083/jcb.151.2.413
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发表时间：
2000-10-16
期刊：
影响因子：
--
通讯作者：
Cohen FS
中科院分区：
文献类型：
--
作者：
Melikyan GB;Markosyan RM;Hemmati H;Delmedico MK;Lambert DM;Cohen FS
许多病毒融合蛋白以六螺旋束为核心结构。研究了 HIV 包膜诱导的融合，以确定膜合并是由于转变为束结构还是在束形成后发生。使用次优温度来阻止中间阶段的融合。当在此阶段通过添加抑制肽来阻止束形成时，膜在升高温度时不会融合。相反，当通过在中间将溶血磷脂酰胆碱（LPC）掺入细胞膜来阻止膜合并时，在优化温度时不会形成束。在没有 LPC 的情况下，当中间体的温度升高时间太短而无法促进融合时，六螺旋束不会形成。动力学测量表明，在温度脉冲之后，细胞并未进一步走向融合。后面的结果表明束形成是被捕获的中间体和融合之间的限速步骤。电测量表明，HIV 包膜诱导的孔最初很大并且生长迅速。有人提出，束的形成和融合彼此依赖，并且 Env 在转变为六螺旋束期间的运动直接诱导膜融合的脂质重排。由于肽抑制表明，在中间阶段，gp41 的七肽重复序列已稳定暴露，因此中间体的产生对于药物和/或疫苗开发可能具有重要意义。
Many viral fusion proteins exhibit a six-helix bundle as a core structure. HIV Env–induced fusion was studied to resolve whether membrane merger was due to the transition into the bundle configuration or occurred after bundle formation. Suboptimal temperature was used to arrest fusion at an intermediate stage. When bundle formation was prevented by adding inhibitory peptides at this stage, membranes did not merge upon raising temperature. Inversely, when membrane merger was prevented by incorporating lysophosphatidylcholine (LPC) into cell membranes at the intermediate, the bundle did not form upon optimizing temperature. In the absence of LPC, the six-helix bundle did not form when the temperature of the intermediate was raised for times too short to promote fusion. Kinetic measures showed that after the temperature pulse, cells had not advanced further toward fusion. The latter results indicate that bundle formation is the rate-limiting step between the arrested intermediate and fusion. Electrical measures showed that the HIV Env–induced pore is initially large and grows rapidly. It is proposed that bundle formation and fusion are each contingent on the other and that movement of Env during its transition into the six-helix bundle directly induces the lipid rearrangements of membrane fusion. Because peptide inhibition showed that, at the intermediate stage, the heptad repeats of gp41 have become stably exposed, creation of the intermediate could be of importance in drug and/or vaccine development.
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影响因子：
56.9
作者：
LaCasse, RA;Follis, KE;Nunberg, JH
通讯作者：
Nunberg, JH
DOI：
10.1084/jem.172.4.1233
发表时间：
1990-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Healey D;Dianda L;Moore JP;McDougal JS;Moore MJ;Estess P;Buck D;Kwong PD;Beverley PC;Sattentau QJ
通讯作者：
Sattentau QJ
影响因子：
64.5
作者：
Eckert, DM;Malashkevich, VN;Kim, PS
通讯作者：
Kim, PS
影响因子：
2.9
作者：
EDELHOCH, H
通讯作者：
EDELHOCH, H
影响因子：
1.5
作者：
JONAK, ZL;CLARK, RK;DEBOUCK, C
通讯作者：
DEBOUCK, C