内体分选转运复合体-I（ESCRT-I）核心结构及内体分选转运复合体-II（ESCRT-II）黏合结构域揭示了黏合结构域在连接ESCRT-I与膜中的作用。

ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes.

作者信息

Teo Hsiangling, Gill David J, Sun Ji, Perisic Olga, Veprintsev Dmitry B, Vallis Yvonne, Emr Scott D, Williams Roger L

机构信息

MRC Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge, CB2 2QH, United Kingdom.

出版信息

Cell. 2006 Apr 7;125(1):99-111. doi: 10.1016/j.cell.2006.01.047.

DOI:10.1016/j.cell.2006.01.047

PMID:16615893

Abstract

ESCRT complexes form the main machinery driving protein sorting from endosomes to lysosomes. Currently, the picture regarding assembly of ESCRTs on endosomes is incomplete. The structure of the conserved heterotrimeric ESCRT-I core presented here shows a fan-like arrangement of three helical hairpins, each corresponding to a different subunit. Vps23/Tsg101 is the central hairpin sandwiched between the other subunits, explaining the critical role of its "steadiness box" in the stability of ESCRT-I. We show that yeast ESCRT-I links directly to ESCRT-II, through a tight interaction of Vps28 (ESCRT-I) with the yeast-specific zinc-finger insertion within the GLUE domain of Vps36 (ESCRT-II). The crystal structure of the GLUE domain missing this insertion reveals it is a split PH domain, with a noncanonical lipid binding pocket that binds PtdIns3P. The simultaneous and reinforcing interactions of ESCRT-II GLUE domain with membranes, ESCRT-I, and ubiquitin are critical for ubiquitinated cargo progression from early to late endosomes.

摘要

内体分选转运复合体（ESCRT）形成了驱动蛋白质从内体向溶酶体进行分选的主要机制。目前，关于ESCRT在内体上组装的情况尚不完整。此处展示的保守异源三聚体ESCRT-I核心结构呈现出三个螺旋发夹的扇形排列，每个螺旋发夹对应一个不同的亚基。Vps23/Tsg101是夹在其他亚基之间的中央发夹，这解释了其“稳定盒”在ESCRT-I稳定性中的关键作用。我们发现酵母ESCRT-I通过Vps28（ESCRT-I）与Vps36（ESCRT-II）的GLUE结构域内酵母特异性锌指插入片段的紧密相互作用直接与ESCRT-II相连。缺少该插入片段的GLUE结构域的晶体结构显示它是一个分裂的PH结构域，具有一个结合磷脂酰肌醇-3-磷酸（PtdIns3P）的非典型脂质结合口袋。ESCRT-II的GLUE结构域与膜、ESCRT-I和泛素同时发生且相互增强的相互作用对于泛素化货物从早期内体向晚期内体的转运至关重要。