Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase.
Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase.
复制标题
DOI：
10.1016/j.str.2010.01.020
复制
发表时间：
2010-03-14
期刊：
影响因子：
--
通讯作者：
Forman-Kay JD
中科院分区：
文献类型：
--
作者：
Mittag T;Marsh J;Grishaev A;Orlicky S;Lin H;Sicheri F;Tyers M;Forman-Kay JD
内含子无序蛋白可以与伴侣蛋白形成高度动态的复合物。一个这样的动态复合物涉及内在无序的Sic 1与其合作伙伴Cdc 4在酵母细胞周期进程的调节。六个N-末端Sic 1位点的磷酸化导致每个磷酸化位点与泛素连接酶的底物识别亚基Cdc 4中的初级结合口袋的平衡接合。利用实验NMR和小角X射线散射数据的合奏计算揭示了显着的瞬态结构，在两个磷酸化状态的隔离合奏（Sic 1和pSic 1），调制他们的静电势，建议的结构基础上提出的强大贡献的静电结合。动态pSic 1-Cdc 4复合物的结构模型展示了泛素连接酶复合物中的空间排列。这些结果提供了一个蛋白质，主要是无序在其自由和结合状态的物理图片，使其结构/功能关系的方面得到阐明。
Intrinsically disordered proteins can form highly dynamic complexes with partner proteins. One such dynamic complex involves the intrinsically disordered Sic1 with its partner Cdc4 in regulation of yeast cell cycle progression. Phosphorylation of six N-terminal Sic1 sites leads to equilibrium engagement of each phosphorylation site with the primary binding pocket in Cdc4, the substrate recognition subunit of a ubiquitin ligase. ENSEMBLE calculations utilizing experimental NMR and small-angle x-ray scattering data reveal significant transient structure in both phosphorylation states of the isolated ensembles (Sic1 and pSic1) that modulates their electrostatic potential, suggesting a structural basis for the proposed strong contribution of electrostatics to binding. A structural model of the dynamic pSic1-Cdc4 complex demonstrates the spatial arrangements in the ubiquitin ligase complex. These results provide a physical picture of a protein that is predominantly disordered in both its free and bound states, enabling aspects of its structure/function relationship to be elucidated.
登录
查看更多内容
Cullin环E3连接酶机械中泛素化的机制：底物方向的构象控制。
影响因子：
4.3
作者：
Liu J;Nussinov R
通讯作者：
Nussinov R
影响因子：
64.5
作者：
Duda, David M.;Borg, Laura A.;Scott, Daniel C.;Hunt, Harold W.;Hammel, Michal;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
影响因子：
56.9
作者：
Klein-Seetharaman, J;Oikawa, M;Schwalbe, H
通讯作者：
Schwalbe, H
影响因子：
5.6
作者：
De Guzman, RN;Goto, NK;Wright, PE
通讯作者：
Wright, PE
影响因子：
6.8
作者：
Eliezer, David
通讯作者：
Eliezer, David