Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex
Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex
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DOI：
10.1016/j.devcel.2008.04.004
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发表时间：
2008-06-01
影响因子：
11.8
通讯作者：
Hurley, James H.
中科院分区：
文献类型：
--
作者：
Im, Young Jun;Hurley, James H.
ESCRT-II在受体下调和多泡体生物发生中起着关键作用，并且从酵母到人类都是保守的。两个人的ESCRT-II复合物结构的晶体结构已被确定在2.6和2.9埃的分辨率，分别。该复合物具有三个叶，并且包含VPS 22和VPS 36各一个拷贝以及VPS 25的两个拷贝。该结构揭示了一个动态螺旋结构域，VPS 22和VPS 36亚基都对该结构域有贡献，该结构域将GLUE结构域连接到ESCRT-II核心的其余部分。流体动力学分析表明，完整的ESCRT-II具有紧凑，封闭的构象。ESCRT-II通过紧邻VPS 36-GLUE结构域C-末端的螺旋与ESCRT-I VPS 28 C-末端结构域亚基结合。ESCRT-II通过Vps 36 GLUE结构域和Vps 22的第一螺旋的脂质结合活性靶向内体膜。这些数据为ESCRT-II复合物提供了一个统一的结构和功能框架。
ESCRT-II plays a pivotal role in receptor downregulation and multivesicular body biogenesis and is conserved from yeast to humans. The crystal structures of two human ESCRT-II complex structures have been determined at 2.6 and 2.9 angstrom resolution, respectively. The complex has three lobes and contains one copy each of VPS22 and VPS36 and two copies of VPS25. The structure reveals a dynamic helical domain to which both the VPS22 and VPS36 subunits contribute that connects the GLUE domain to the rest of the ESCRT-II core. Hydrodynamic analysis shows that intact ESCRT-II has a compact, closed conformation. ESCRT-II binds to the ESCRT-I VPS28 C-terminal domain subunit through a helix immediately C-terminal to the VPS36-GLUE domain. ESCRT-II is targeted to endosomal membranes by the lipid-binding activities of both the Vps36 GLUE domain and the first helix of Vps22. These data provide a unifying structural and functional framework for the ESCRT-II complex.