Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1.
Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1.
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DOI：
10.1083/jcb.200803110
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发表时间：
2008-09-08
影响因子：
7.8
通讯作者：
Macara, Ian G.
中科院分区：
文献类型：
--
作者：
Hao, Yi;Macara, Ian G.
RCC 1是Ran鸟苷三磷酸酶的唯一已知交换因子，在核运输、纺锤体组织和核膜形成中起重要作用。RCC 1通过与DNA和组蛋白的双峰连接与染色质结合，结合缺陷导致染色体错误分离。染色质结合被apo-Ran增强。然而，这种调节的机制尚不清楚。我们现在证明，RCC 1的N-末端尾是必不可少的协会与DNA，但抑制组蛋白结合。Apo-Ran显著促进RCC 1与DNA和组蛋白的结合，并且这些作用是尾部介导的。使用荧光共振能量转移生物传感器，我们检测到的构象变化，在尾部的RCC 1耦合到两个结合模式，并响应与Ran和importin-α的相互作用。该生物传感器还报告了活细胞中伴随有丝分裂的变化。我们建议，然诱导变构构象开关的尾巴，暴露组蛋白结合表面的RCC 1和促进协会的带正电荷的尾巴与DNA。
RCC1 is the only known exchange factor for the Ran guanosine triphosphatase and performs essential roles in nuclear transport, spindle organization, and nuclear envelope formation. RCC1 binds to chromatin through a bimodal attachment to DNA and histones, and defects in binding cause chromosome missegregation. Chromatin binding is enhanced by apo-Ran. However, the mechanism underlying this regulation has been unclear. We now demonstrate that the N-terminal tail of RCC1 is essential for association with DNA but inhibits histone binding. Apo-Ran significantly promotes RCC1 binding to both DNA and histones, and these effects are tail mediated. Using a fluorescence resonance energy transfer biosensor, we detect conformational changes in the tail of RCC1 coupled to the two binding modes and in response to interactions with Ran and importin-α. The biosensor also reports changes accompanying mitosis in living cells. We propose that Ran induces an allosteric conformational switch in the tail that exposes the histone-binding surface on RCC1 and facilitates association of the positively charged tail with DNA.
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影响因子：
5.6
作者：
LUTTER, LC
通讯作者：
LUTTER, LC
影响因子：
3.3
作者：
Silverman-Gavrila, RV;Wilde, A
通讯作者：
Wilde, A
影响因子：
64.8
作者：
Carazo-Salas, RE;Guarguaglini, G;Mattaj, IW
通讯作者：
Mattaj, IW
RAN交换因子RCC1的核进口至少由两种不同的机制介导。
影响因子：
7.8
作者：
Nemergut, M E;Macara, I G
通讯作者：
Macara, I G
影响因子：
64.8
作者：
Renault, L;Nassar, N;Wittinghofer, A
通讯作者：
Wittinghofer, A