Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4
Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4
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DOI：
10.1038/nature06171
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发表时间：
2007-10-11
期刊：
影响因子：
64.8
通讯作者：
Williams, Roger L.
中科院分区：
文献类型：
--
作者：
Obita, Takayuki;Saksena, Suraj;Williams, Roger L.
AAA+ atp酶对于细胞膜运输、细胞器生物发生、DNA复制、细胞内运动、细胞骨架重塑、蛋白质折叠和蛋白质水解等多种活动至关重要(1)。AAA atp酶Vps4是内体向溶酶体运输的核心（2,3），逆转录病毒出芽(4)和细胞分裂(5)，从膜上解离ESCRT复合物（运输所需的内体分选复合物）（6-15）。本研究表明，在酵母中6个escrt - iii相关亚基中，只有Vps2和Did2结合Vps4的MIT（微管相互作用和运输）结构域，并且亚基的羧基末端30残基是相互作用的必要和充分条件。我们确定了Vps2 C末端与Vps4 MIT结构域复合物的晶体结构，解释了选择性ESCRT-III识别的基础。MIT螺旋α 2和α 3识别（D/E） xxLxxRLxxL（K/R）基序，该基序内的突变导致酵母的分选缺陷。我们对一个功能未知的古细菌AAA atp酶氨基末端结构域的晶体结构表明，它与Vps4的MIT结构域密切相关。古细菌atp酶与古细菌ESCRT-III样蛋白相互作用，尽管这些生物没有内膜系统，这表明Vps4/ESCRT-III伙伴关系是真核生物和古细菌分化之前功能的遗迹。
The AAA+ ATPases are essential for various activities such as membrane trafficking, organelle biogenesis, DNA replication, intracellular locomotion, cytoskeletal remodelling, protein folding and proteolysis(1). The AAA ATPase Vps4, which is central to endosomal traffic to lysosomes(2,3), retroviral budding(4) and cytokinesis(5), dissociates ESCRT complexes (the endosomal sorting complexes required for transport) from membranes(6-15). Here we show that, of the six ESCRT-III-related subunits in yeast, only Vps2 and Did2 bind the MIT (microtubule interacting and transport) domain of Vps4, and that the carboxy-terminal 30 residues of the subunits are both necessary and sufficient for interaction. We determined the crystal structure of the Vps2 C terminus in a complex with the Vps4 MIT domain, explaining the basis for selective ESCRT-III recognition. MIT helices alpha 2 and alpha 3 recognize a (D/E) xxLxxRLxxL(K/R) motif, and mutations within this motif cause sorting defects in yeast. Our crystal structure of the amino-terminal domain of an archaeal AAA ATPase of unknown function shows that it is closely related to the MIT domain of Vps4. The archaeal ATPase interacts with an archaeal ESCRT-III-like protein even though these organisms have no endomembrane system, suggesting that the Vps4/ESCRT-III partnership is a relic of a function that pre-dates the divergence of eukaryotes and Archaea.