Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5
Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5
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DOI：
10.1038/nsmb1064
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发表时间：
2006-03-01
影响因子：
16.8
通讯作者：
Hurley, JH
中科院分区：
文献类型：
--
作者：
Lee, S;Tsai, YC;Hurley, JH
Rabex-5是Rab 5的交换因子，Rab 5是内体运输的主要调节因子。Rabex-5结合单泛素，经历共价泛素化并含有内在的泛素连接酶活性，所有这些都需要N-末端A20锌指，紧接着是螺旋。在2.5埃分辨率下结合到泛素的Rabex-5的N-末端部分的结构显示Rabex-5-泛素相互作用发生在两个位点。第一个位点是一种新型的泛素结合结构域，一种反向的泛素相互作用基序，它以类似于29 μ M的亲和力结合到泛素上的典型IIe 44疏水补丁。第二个是A20锌指上的二芳补丁，其以类似于22 μ M的亲和力结合到以泛素的Asp 58为中心的极性区域。A20锌指二芳族补丁介导的泛素连接酶的活性，直接招募泛素负载的泛素缀合酶。
Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and contains an intrinsic ubiquitin ligase activity, all of which require an N-terminal A20 zinc finger followed immediately by a helix. The structure of the N-terminal portion of Rabex-5 bound to ubiquitin at 2.5-angstrom resolution shows that Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which binds with similar to 29-mu M affinity to the canonical IIe44 hydrophobic patch on ubiquitin. The second is a diaromatic patch on the A20 zinc finger, which binds with similar to 22-mu M affinity to a polar region centered on Asp58 of ubiquitin. The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme.