The structural basis of tail-anchored membrane protein recognition by Get3.
The structural basis of tail-anchored membrane protein recognition by Get3.
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DOI：
10.1038/nature08319
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发表时间：
2009-09-17
期刊：
影响因子：
64.8
通讯作者：
Keenan RJ
中科院分区：
文献类型：
--
作者：
Mateja A;Szlachcic A;Downing ME;Dobosz M;Mariappan M;Hegde RS;Keenan RJ
新合成的膜蛋白靶向内质网是一个重要的细胞过程。大多数膜蛋白被信号识别粒子识别和靶向共翻译。然而，近5%的膜蛋白被单个羧基末端跨膜结构域“尾部锚定”，不能进入共翻译途径。相反，尾巴锚定蛋白在翻译后被称为Get3的保守atp酶靶向。尾巴锚定蛋白识别或Get3靶向的机制基础尚不清楚。在这里，我们展示了酵母Get3在“开放”（无核苷酸）和“封闭”（ADP·AlF 4−结合）二聚体状态下的晶体结构。在封闭状态下，Get3的二聚体界面包含一个巨大的疏水沟槽，这与尾巴锚定蛋白结合的突变分析有关。在开放状态下，Get3经历了惊人的重排，破坏了沟槽并屏蔽了其疏水表面。这些数据为尾锚蛋白在Get3靶向膜过程中核苷酸调控的结合和释放提供了分子机制。
Targeting of newly synthesized membrane proteins to the endoplasmic reticulum is an essential cellular process. Most membrane proteins are recognized and targeted co-translationally by the signal recognition particle. However, nearly 5% of membrane proteins are ‘tail-anchored’ by a single carboxy-terminal transmembrane domain that cannot access the co-translational pathway. Instead, tail-anchored proteins are targeted post-translationally by a conserved ATPase termed Get3. The mechanistic basis for tail-anchored protein recognition or targeting by Get3 is not known. Here we present crystal structures of yeast Get3 in ‘open’ (nucleotide-free) and ‘closed’ (ADP·AlF 4−-bound) dimer states. In the closed state, the dimer interface of Get3 contains an enormous hydrophobic groove implicated by mutational analyses in tail-anchored protein binding. In the open state, Get3 undergoes a striking rearrangement that disrupts the groove and shields its hydrophobic surfaces. These data provide a molecular mechanism for nucleotide-regulated binding and release of tail-anchored proteins during their membrane targeting by Get3.
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影响因子：
56.9
作者：
GEORGIADIS, MM;KOMIYA, H;REES, DC
通讯作者：
REES, DC
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.8
作者：
Montoya, G;Svensson, C;Sinning, I
通讯作者：
Sinning, I
影响因子：
4.8
作者：
Kuroda, R;Ikenoue, T;Ito, A
通讯作者：
Ito, A
影响因子：
3.3
作者：
Horie, C;Suzuki, H;Mihara, K
通讯作者：
Mihara, K