Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1
Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1
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DOI：
10.1016/j.molcel.2004.12.020
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发表时间：
2005-02-04
期刊：
影响因子：
16
通讯作者：
Schulman, BA
中科院分区：
文献类型：
--
作者：
Huang, DT;Paydar, A;Schulman, BA
E2结合酶在泛素和泛素样蛋白(Ublp)的转移级联中起着核心作用：E2接受来自e1酶的ublp，然后E2经常与E3酶相互作用，促进ublp向靶位的转移。本文报道了NEDD8‘S异二聚体E1的C-末端结构域与NEDD8’S的催化核心区UBC12之间的配合物的晶体结构。结构和相关的突变分析揭示了NEDD8的S E1招募Ubc12的分子细节。有趣的是，E1‘S的Ubc12结合域类似于泛素，并以模仿泛素与泛素结合域的相互作用的方式招募Ubc12。与E2-E3复合体的结构比较表明，Ubc12上的EL和E3结合部位可能重叠，增加了E1和E3与E2相互作用的串扰可能影响uBLP转移的特异性和可操作性的可能性。
E2 conjugating enzymes play a central role in ubiquitin and ubiquitin-like protein (ublp) transfer cascades: the E2 accepts the ublp from the E1 enzyme and then the E2 often interacts with an E3 enzyme to promote ublp transfer to the target. We report here the crystal structure of a complex between the C-terminal domain from NEDD8's heterodimeric E1 (APPBP1-UBA3) and the catalytic core domain of NEDD8's E2 (Ubc12). The structure and associated mutational analyses reveal molecular details of Ubc12 recruitment by NEDD8's E1. Interestingly, the E1's Ubc12 binding domain resembles ubiquitin and recruits Ubc12 in a manner mimicking ubiquitin's interactions with ubiquitin binding domains. Structural comparison with E2-E3 complexes indicates that the El and E3 binding sites on Ubc12 may overlap and raises the possibility that cross-talk between E1 and E3 interacting with an E2 could influence the specificity and processivity of ublp transfer.