Structure and catalytic activation of the TRIM23 RING E3 ubiquitin ligase.

Structure and catalytic activation of the TRIM23 RING E3 ubiquitin ligase.
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DOI:
10.1002/prot.25348
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发表时间:
2017-10
期刊:
影响因子:
2.9
通讯作者:
Pornillos O
Pornillos O
中科院分区:
生物学4区
文献类型:
--
作者:
Dawidziak DM;Sanchez JG;Wagner JM;Ganser-Pornillos BK;Pornillos O

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三元基序(TRIM)蛋白包括一个大家族的环型泛素E3连接酶,调节重要的生物过程。一个新兴的一般模型是TRIMs形成了细长的反平行线圈状二聚体,阻止了两个伴随的RING结构域的相互作用。RING结构域本身以二聚体的形式结合E2偶联酶,这意味着一个活跃的TRIM连接酶需要高阶低聚的基础螺旋状二聚体。在这里,我们报道了TRIM23 RING结构域的分离晶体结构和与e2 -泛素缀合物的复合物。我们的研究结果表明,TRIM23的酶活性需要环二聚化,与TRIM激活的一般模型一致。
Tripartite motif (TRIM) proteins comprise a large family of RING-type ubiquitin E3 ligases that regulate important biological processes. An emerging general model is that TRIMs form elongated antiparallel coiled-coil dimers that prevent interaction of the two attendant RING domains. The RING domains themselves bind E2 conjugating enzymes as dimers, implying that an active TRIM ligase requires higher-order oligomerization of the basal coiled-coil dimers. Here, we report crystal structures of the TRIM23 RING domain in isolation and in complex with an E2-ubiquitin conjugate. Our results indicate that TRIM23 enzymatic activity requires RING dimerization, consistent with the general model of TRIM activation.
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