Sedimentation velocity studies of the high-molecular weight aggregates of the HIV gp41 ectodomain.
Sedimentation velocity studies of the high-molecular weight aggregates of the HIV gp41 ectodomain.
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HIV gp41 胞外域高分子量聚集体的沉降速度研究。
DOI：
10.1110/ps.04916704
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Caffrey,Michael
中科院分区：
文献类型：
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作者：
Jacobs,Amy;Hartman,Kari;Laue,Thomas;Caffrey,Michael
HIV包膜蛋白gp41在HIV相关痴呆患者的脑组织中蓄积。以前，我们已经通过电子显微镜显示，SIV gp41的胞外结构域，这是类似于HIV的，在体外形成高分子量聚集体，我们已经假设，这种高分子量聚集体是负责神经损伤的方式类似于蛋白质沉积疾病，如阿尔茨海默氏症和朊病毒疾病。在这篇手稿中，我们通过沉降速度表征了HIV gp41胞外域的自缔合。我们发现，存在gp41高分子量聚集体的离散物种。最大群体发生在20 S时，这对应于gp41的105个三聚体，表明高分子量聚集体的成核需要5个三聚体。gp41自缔合的浓度依赖性表明它通过质量作用发生。gp41自缔合的温度依赖性表明它是由熵驱动的，表明gp41三聚体之间的分子间疏水相互作用正在驱动缔合。
Accumulation of the HIV envelope protein gp41 is observed in the brain tissues of patients suffering from HIV‐associated dementia. Previously, we have shown by electron microscopy that the extracellular domain of SIV gp41, which is analogous to that of HIV, forms high–molecular weight aggregates in vitro, and we have postulated that such high–molecular weight aggregates are responsible for neurological damage in a manner similar to protein deposition diseases such as Alzheimer's and the prion diseases. In this manuscript, we have characterized the self‐association of the HIV gp41 ectodomain by sedimentation velocity. We show that discreet species of the gp41 high–molecular weight aggregates are present. The maximum population occurs at 20 S, which corresponds to ∼5 trimers of gp41, suggesting that five trimers are required for nucleation of the high–molecular weight aggregates. The concentration dependence of the gp41 self‐association indicates that it occurs by mass action. The temperature dependence of gp41 self‐association suggests that it is driven by entropy, indicating that intermolecular hydrophobic interactions between trimers of gp41 are driving the association.