多亚基 tethering 复合物 Dsl1 捕获囊泡的基于结构的机制。
A structure-based mechanism for vesicle capture by the multisubunit tethering complex Dsl1.
机构信息
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
出版信息
Cell. 2009 Dec 11;139(6):1119-29. doi: 10.1016/j.cell.2009.11.002.
Abstract
Vesicle trafficking requires membrane fusion, mediated by SNARE proteins, and upstream events that probably include "tethering," an initial long-range attachment between a vesicle and its target organelle. Among the factors proposed to mediate tethering are a set of multisubunit tethering complexes (MTCs). The Dsl1 complex, with only three subunits, is the simplest known MTC and is essential for the retrograde traffic of COPI-coated vesicles from the Golgi to the ER. To elucidate structural principles underlying MTC function, we have determined the structure of the Dsl1 complex, revealing a tower containing at its base the binding sites for two ER SNAREs and at its tip a flexible lasso for capturing vesicles. The Dsl1 complex binds to individual SNAREs via their N-terminal regulatory domains and also to assembled SNARE complexes; moreover, it is capable of accelerating SNARE complex assembly. Our results suggest that even the simplest MTC may be capable of orchestrating vesicle capture, uncoating, and fusion.
摘要
囊泡运输需要膜融合，由 SNARE 蛋白介导，上游事件可能包括“系留”，即囊泡与其靶细胞器之间的初始远距离附着。被提议介导系留的因素之一是一组多亚基系留复合物 (MTC)。Dsl1 复合物只有三个亚基，是已知最简单的 MTC，对 COPI 包被囊泡从高尔基体逆行运输到 ER 是必不可少的。为了阐明 MTC 功能的结构原理，我们已经确定了 Dsl1 复合物的结构，揭示了一个包含其底部两个 ER SNARE 结合位点和顶部用于捕获囊泡的灵活套索的塔。Dsl1 复合物通过其 N 端调节结构域与单个 SNARE 结合，也与组装的 SNARE 复合物结合；此外，它能够加速 SNARE 复合物的组装。我们的结果表明，即使是最简单的 MTC 也可能能够协调囊泡捕获、脱壳和融合。
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