Structure and stability of cohesin's Smc1-kleisin interaction
Structure and stability of cohesin's Smc1-kleisin interaction
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DOI：
10.1016/j.molcel.2004.08.030
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发表时间：
2004-09-24
期刊：
影响因子：
16
通讯作者：
Löwe, J
中科院分区：
文献类型：
--
作者：
Haering, CH;Schoffnegger, D;Löwe, J
一种称为粘附素的多亚单位复合体形成了一个巨大的环状结构，可能是通过在复制后捕获姐妹DNA来调节姐妹染色单体的凝聚力。粘附素的Kleisin亚基Scc1完成了环，连接了V形Smc1/3异源二聚体的ABC样ATPase头部。分离酶对Scc1的蛋白水解性切割可能通过破坏Scc1桥来触发姐妹染色单体的分离。SMC-kleisin桥的一半由Smc1‘S ATPase与Scc1’S C-末端结构域的晶体结构揭示。后者形成一个有翼的螺旋，与SMC1的S ATPase头部的一对P链结合在一起。接触界面保守残基的突变破坏了Scc1‘S与Smc1/3异源二聚体的相互作用，并消除了粘附素功能。Scc1‘S N端与Smc3的相互作用依赖于先前的C端与Smc1的连接。体内粘附素复合体中Smc1-Scc1相互作用很少或没有转换，因为DNA复制后表达的不可切割的Scc1不会阻碍后期。
A multisubunit complex called cohesin forms a huge ring structure that mediates sister chromatid cohesion, possibly by entrapping sister DNAs following replication. Cohesin's kleisin subunit Scc1 completes the ring, connecting the ABC-like ATPase heads of a V-shaped Smc1/3 heterodimer. Proteolytic cleavage of Scc1 by separase triggers sister chromatid disjunction, presumably by breaking the Scc1 bridge. One half of the SMC-kleisin bridge is revealed here by a crystal structure of Smc1's ATPase complexed with Scc1's C-terminal domain. The latter forms a winged helix that binds a pair of P strands in Smc1's ATPase head. Mutation of conserved residues within the contact interface destroys Scc1's interaction with Smc1/3 heterodimers and eliminates cohesin function. Interaction of Scc1's N terminus with Smc3 depends on prior C terminus connection with Smc1. There is little or no turnover of Smc1-Scc1 interactions within cohesin complexes in vivo because expression of noncleavable Scc1 after DNA replication does not hinder anaphase.