RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.
RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.
复制标题
DOI：
10.1016/j.jmb.2010.03.037
复制
发表时间：
2010-05-14
影响因子：
5.6
通讯作者：
Tan S
中科院分区：
文献类型：
--
作者：
England JR;Huang J;Jennings MJ;Makde RD;Tan S
RCC 1（染色体凝聚调节因子）与染色质的结合对于细胞过程如有丝分裂、核质转运和核膜形成至关重要，因为RCC 1将小的GTP酶Ran募集到染色质并在染色体周围建立Ran-GTP梯度。然而，RCC 1与核小体（染色质的重复单位）结合的分子机制尚不清楚。我们已经使用生物化学方法来测试RCC 1 β-螺旋桨蛋白如何与核小体结合的结构模型。与流行的模型相反，RCC 1似乎没有使用与其Ran结合面相对的β螺旋桨面来与核小体相互作用。相反，我们发现，RCC 1使用一个构象灵活的环区域，我们称之为之字形循环，除了其N-末端尾巴结合到核小体。RCC 1之字形环与其Ran结合表面的并列表明了核小体结合RCC 1如何将Ran招募到染色质的新机制。此外，该模型解释了先前无法解释的观察结果，即Ran如何与RCC 1依赖和独立的核小体相互作用，以及核小体的结合如何增强RCC 1的Ran核苷酸交换活性。
The binding of RCC1 (Regulator of Chromosome Condensation) to chromatin is critical for cellular processes such as mitosis, nucleocytoplasmic transport and nuclear envelope formation because RCC1 recruits the small GTPase Ran to chromatin and sets up a Ran-GTP gradient around the chromosomes. However, the molecular mechanism by which RCC1 binds to nucleosomes, the repeating unit of chromatin, is not known. We have used biochemical approaches to test structural models for how the RCC1 β-propeller protein could bind to the nucleosome. In contrast to the prevailing model, RCC1 does not appear to use the β-propeller face opposite to its Ran-binding face to interact with nucleosomes. Instead, we find that RCC1 uses a conformationally flexible loop region we have termed the switchback loop in addition to its N-terminal tail to bind to the nucleosome. The juxtaposition of the RCC1 switchback loop to its Ran binding surface suggests a novel mechanism for how nucleosome-bound RCC1 recruits Ran to chromatin. Furthermore, this model accounts for previously unexplained observations for how Ran can interact with the nucleosome both dependent and independent of RCC1, and how binding of the nucleosome can enhance RCC1’s Ran nucleotide exchange activity.
登录
查看更多内容
影响因子：
5.8
作者：
Keppler BR;Archer TK
通讯作者：
Archer TK
影响因子：
5.6
作者：
Lowary, PT;Widom, J
通讯作者：
Widom, J
RCC1蛋白是染色体凝结发作的调节剂，位于细胞核中并与DNA结合。
影响因子：
7.8
作者：
Ohtsubo, M;Okazaki, H;Nishimoto, T
通讯作者：
Nishimoto, T
影响因子：
64.8
作者：
Renault, L;Nassar, N;Wittinghofer, A
通讯作者：
Wittinghofer, A
影响因子：
64.5
作者：
Orlicky, S;Tang, XJ;Sicheri, F
通讯作者：
Sicheri, F