Bimodal activation of SMC ATPase by intra- and inter-molecular interactions
Bimodal activation of SMC ATPase by intra- and inter-molecular interactions
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DOI：
10.1093/emboj/20.12.3238
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发表时间：
2001-06-15
期刊：
影响因子：
11.4
通讯作者：
Hirano, T
中科院分区：
文献类型：
--
作者：
Hirano, M;Anderson, DE;Hirano, T
染色体的结构维持（SMC）蛋白在从细菌到人类的高阶染色体动力学中起着至关重要的作用，有人提出枯草芽孢杆菌SMC （BsSMC）同型二聚体由两个反平行的螺旋状旋臂组成，每个旋臂在其远端具有一个atp结合域。然而，双臂结构如何支持BsSMC依赖atp的作用仍然是完全未知的，通过构建包括“单臂”BsSMC在内的许多突变衍生物，我们在这里展示了中心铰链域提供了允许双臂打开和关闭的结构灵活性，这种独特的结构带来了SMC atp酶周期的双峰调节。关闭臂可以通过允许二聚体内的端-端相互作用（分子内模式）触发ATP水解。当与DNA结合时，ATP促进二聚体-二聚体相互作用，进而激活其DNA依赖性ATP酶活性（分子间模式）。我们的研究结果揭示了ATPase调控的新机制，并为真核SMC蛋白复合物如何介导染色体凝聚和姐妹染色单体染色体内聚等多种染色体功能提供了机制见解。
Structural maintenance of chromosomes (SMC) proteins play fundamental roles in higher-order chromosome dynamics from bacteria to humans, It has been proposed that the Bacillus subtilis SMC (BsSMC) homodimer is composed of two anti-parallel coiled-coil arms, each having an ATP-binding domain at its distal end. It remains totally unknown, however, how the two-armed structure supports ATP-dependent actions of BsSMC, By constructing a number of mutant derivatives including 'single-armed' BsSMC, we show here that the central hinge domain provides a structural flexibility that allows opening and closing of the two arms, This unique structure brings about bimodal regulation of the SMC ATPase cycle. Closing the arm can trigger ATP hydrolysis by allowing an end-end interaction within a dimer (intramolecular mode). When bound to DNA, ATP promotes a dimer-dimer interaction, which in turn activates their DNA-dependent ATPase activity (intermolecular mode). Our results reveal a novel mechanism of ATPase regulation and provide mechanistic insights into how eukaryotic SMC protein complexes could mediate diverse chromosomal functions, such as chromosome condensation and sister chromatid chromosome cohesion.