TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other TRIM family members.

TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other TRIM family members.
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DOI:
10.1371/journal.pone.0037470
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Cheung BB
Cheung BB
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bell JL;Malyukova A;Holien JK;Koach J;Parker MW;Kavallaris M;Marshall GM;Cheung BB

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TRIM蛋白家族以其三部分基序(TRIM)而区别于其他蛋白。通常,TRIM蛋白含有一个环指结构域、一个或两个B-box结构域、一个卷曲结构域和更多可变的C-末端结构域。TRIM16没有环状结构域,但含有两个B-box结构域。在这里,我们发现TRIM16通过其螺旋卷曲结构域均二聚体,并与其他TRIM家族成员TRIM24、早幼粒细胞白血病(PML)蛋白和中线-1(MID1)异二聚体。虽然TRIM16没有经典的环状结构域,但对TRIM16的三维模拟表明其B-盒结构域采用环状折叠,从而导致了TRIM16作为泛素连接酶的假说。与这一假设一致,我们在体内和体外实验中证明了TRIM16具有自身泛素化活性,并作为E3泛素连接酶。因此,通过其独特的结构,TRIM16既具有与其他TRIM蛋白的异源二聚功能,又具有E3泛素连接酶活性。
The TRIM family of proteins is distinguished by its tripartite motif (TRIM). Typically, TRIM proteins contain a RING finger domain, one or two B-box domains, a coiled-coil domain and the more variable C-terminal domains. TRIM16 does not have a RING domain but does harbour two B-box domains. Here we showed that TRIM16 homodimerized through its coiled-coil domain and heterodimerized with other TRIM family members; TRIM24, Promyelocytic leukaemia (PML) protein and Midline-1 (MID1). Although, TRIM16 has no classic RING domain, three-dimensional modelling of TRIM16 suggested that its B-box domains adopts RING-like folds leading to the hypothesis that TRIM16 acts as an ubiquitin ligase. Consistent with this hypothesis, we demonstrated that TRIM16, devoid of a classical RING domain had auto-polyubiquitination activity and acted as an E3 ubiquitin ligase in vivo and in vitro assays. Thus via its unique structure, TRIM16 possesses both heterodimerization function with other TRIM proteins and also has E3 ubiquitin ligase activity.
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