Structure of the MID1 tandem B-boxes reveals an interaction reminiscent of intermolecular ring heterodimers
Structure of the MID1 tandem B-boxes reveals an interaction reminiscent of intermolecular ring heterodimers
复制标题
DOI：
10.1021/bi7018496
复制
发表时间：
2008-02-26
期刊：
影响因子：
2.9
通讯作者：
Massiah, Michael A.
中科院分区：
文献类型：
--
作者：
Tao, Hu;Simmons, Brandi N.;Massiah, Michael A.
由N-末端RING、B-box和卷曲螺旋（RBCC）结构域定义的三重基序（TRIM）蛋白家族由单个2型B-box结构域或I型和2型的串联B-box结构域（131132）组成。在这里，我们报告的第一个结构的B盒结构域在其天然的串联方向。B盒来自Midline-1，一种推定的泛素E3连接酶，其是蛋白磷酸酶2A（PP 2Ac）的催化亚基的蛋白体降解所需的。PP 2Ac的调节亚基Alpha 4与B-box 1的直接结合促进了PP 2Ac的这种功能，而B-box 2似乎影响这种相互作用。都是B盒子和B-box 2在交叉括号基序中结合两个锌原子，并采用类似于RING、PHD、ZZ和U-box结构域的ss ss α结构，尽管它们彼此不同，并且在锌结合残基的间隔上与RING结构域不同。两个B-box结构域相互包装，界面由位于由两个反平行ss链组成的结构环上的残基形成。界面的表面积为188埃（2）（总表面积的17%）。与球状结构一致，T。串联B-box结构域（59 ℃）的温度高于单个结构域，支持B-box I和2结构域之间的稳定相互作用。值得注意的是，这种相互作用让人想起最近确定的RING二聚体的相互作用，这表明B-box 2结构域在调节功能性RING型折叠中具有进化保守作用的可能性。
The tripartite motif (TRIM) protein family, defined by N-terminal RING, B-box, and coiled-coil (RBCC) domains, consists of either a single type 2 B-box domain or tandem B-box domains of type I and type 2 (131132). Here, we report the first structure of the B-box domains in their native tandem orientation. The B-boxes are from Midline-1, a putative ubiquitin E3 ligase that is required for the proteosomal degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). This function of MIDI is facilitated by the direct binding of Alpha4, a regulatory subunit of PP2Ac, to B-box1, while B-box2 appears to influence this interaction. Both B-box. and B-box2 bind two zinc atoms in a cross-brace motif and adopt a similar ss ss alpha structure reminiscent of the RING, PHD, ZZ, and U-box domains, although they differ from each other and with RING domains in the spacing of their zinc-binding residues. The two B-box domains pack against each other with the interface formed by residues located on the structured loop consisting of the two antiparallel ss-strands. The surface area of the interface is 188 angstrom(2) (17% of the total surface). Consistent with the globular structure, the T. of the tandem B-box domain (59 degrees C) is higher than the individual domains, supporting a stable interaction between the B-box I and 2 domains. Notably, the interaction is reminiscent of the interaction of recently determined RING dimers, suggesting the possibility of an evolutionarily conserved role for B-box2 domains in regulating functional RING-type folds.