AIDS virus envelope spike structure

AIDS virus envelope spike structure
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DOI:
10.1016/j.sbi.2007.03.008
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发表时间:
2007-04-01
影响因子:
6.8
通讯作者:
Taylor, Kenneth A.
Taylor, Kenneth A.
中科院分区:
生物学2区
文献类型:
--
作者:
Roux, Kenneth H.;Taylor, Kenneth A.

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HIV-1和密切相关的SIV上的包膜(Env)峰确定了病毒的嗜性,介导了融合过程,并且是体液应答的主要靶标。尽管进行了大量的努力,但Env在揭示其结构和功能秘密方面进展缓慢。三个gp 120亚基组成Env的“头部”,三个gp 41亚基组成“茎部”和其他膜相关元件。最近的描述unliganded(未触发)的gp 120的核心结构,与早期的CD 4配体的原子结构相比,揭示了戏剧性的构象重组的组件,并提出了融合的启动机制。关键V3环的结构,无论是在隔离和与配体的核心,有助于确定其在融合中的作用,并作为中和抗体的主要目标。关于gp 41的结构的其他细节正在出现,因为它从preliganded配置过渡到融合中间体(融合活性或prehairpin中间体)配置,虽然很多仍然是推测性的。冷冻电子断层扫描的最新进展使我们第一次瞥见Env的整体三维结构,当与可用的组件原子结构相匹配时,为三聚体尖峰内的结构元素的组织提供了新的见解。
The envelope (Env) spikes on HIV-1 and closely related SIV define the viral tropism, mediate the fusion process and are the prime target of the humoral response. Despite intensive efforts, Env has been slow to reveal its structural and functional secrets. Three gp120 subunits comprise the 'head' of Env and three gp41 subunits comprise the 'stalk' and other membrane-associated elements. The recent description of the core structure of unliganded (untriggered) gp120, compared to earlier CD4-liganded atomic structures, reveals dramatic conformational reorganization of the components and suggests a mechanism for the initiation of fusion. The structure of the key V3 loop, both in isolation and in association with the liganded core, helps define its role in fusion and as a prime target of neutralizing antibodies. Additional details are emerging regarding the structure of gp41 as it transitions from the preliganded configuration to the fusion intermediate (fusion-active or prehairpin intermediate) configuration, although much remains speculative. Recent advances in cryoelectron tomography are giving us the first glimpses of the overall three-dimensional structure of Env, which, when fitted with the available component atomic structures, provides new insights into the organization of the structural elements within the trimeric spike.