多泡体途径和胞质分裂中 Ist1 功能和 Ist1-Did2 相互作用的结构基础。
Structural basis of Ist1 function and Ist1-Did2 interaction in the multivesicular body pathway and cytokinesis.
机构信息
Life Sciences Institute and Department of Biological Chemistry, Department of Molecular and Integrative Physiology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Mol Biol Cell. 2009 Aug;20(15):3514-24. doi: 10.1091/mbc.e09-05-0403. Epub 2009 May 28.
The ESCRT machinery functions in several important eukaryotic cellular processes. The AAA-ATPase Vps4 catalyzes disassembly of the ESCRT-III complex and may regulate membrane deformation and vesicle scission as well. Ist1 was proposed to be a regulator of Vps4, but its mechanism of action was unclear. The crystal structure of the N-terminal domain of Ist1 (Ist1NTD) reveals an ESCRT-III subunit-like fold, implicating Ist1 as a divergent ESCRT-III family member. Ist1NTD specifically binds to the ESCRT-III subunit Did2, and cocrystallization of Ist1NTD with a Did2 fragment shows that Ist1 interacts with the Did2 C-terminal MIM1 (MIT-interacting motif 1) via a novel MIM-binding structural motif. This arrangement indicates a mechanism for intermolecular ESCRT-III subunit association and may also suggest one form of ESCRT-III subunit autoinhibition via intramolecular interaction.
ESCRT 机制在几种重要的真核细胞过程中发挥作用。AAA-ATP 酶 Vps4 催化 ESCRT-III 复合物的解体，并且可能调节膜变形和囊泡分裂。Ist1 被提议为 Vps4 的调节剂，但其作用机制尚不清楚。Ist1 的 N 端结构域（Ist1NTD）的晶体结构揭示了一个 ESCRT-III 亚基样折叠，暗示 Ist1 是一个不同的 ESCRT-III 家族成员。Ist1NTD 特异性地与 ESCRT-III 亚基 Did2 结合，并且 Ist1NTD 与 Did2 片段的共结晶表明 Ist1 通过一个新的 MIM 结合结构基序与 Did2 C 端 MIM1（MIT 相互作用基序 1）相互作用。这种排列表明了分子间 ESCRT-III 亚基缔合的机制，并且也可能通过分子内相互作用暗示 ESCRT-III 亚基的一种自动抑制形式。
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