Assemblies of structural maintenance of chromosomes (SMC) proteins and kleisin subunits are essential to chromosome organization and segregation across all kingdoms of life. While structural data exist for parts of the SMC-kleisin complexes, complete structures of the entire complexes have yet to be determined, making mechanistic studies difficult. Using an integrative approach that combines crystallographic structural information about the globular subdomains, along with coevolutionary information and an energy landscape optimized force field (AWSEM), we predict atomic-scale structures for several tripartite SMC-kleisin complexes, including prokaryotic condensin, eukaryotic cohesin, and eukaryotic condensin. The molecular dynamics simulations of the SMC-kleisin protein complexes suggest that these complexes exist as a broad conformational ensemble that is made up of different topological isomers. The simulations suggest a critical role for the SMC coiled-coil regions, where the coils intertwine with various linking numbers. The twist and writhe of these braided coils are coupled with the motion of the SMC head domains, suggesting that the complexes may function as topological motors. Opening, closing, and translation along the DNA of the SMC-kleisin protein complexes would allow these motors to couple to the topology of DNA when DNA is entwined with the braided coils.

中文翻译：

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染色体组织蛋白的编织拓扑和能量景观。


染色体结构维持 (SMC) 蛋白和 kleisin 亚基的组装对于所有生命领域的染色体组织和分离至关重要。虽然 SMC-kleisin 复合物的部分结构数据存在，但整个复合物的完整结构尚未确定，这使得机理研究变得困难。使用将球状子域的晶体结构信息与共同进化信息和能量景观优化力场 (AWSSEM) 相结合的综合方法，我们预测了几种三方 SMC-kleisin 复合物的原子尺度结构，包括原核凝聚蛋白、真核凝聚蛋白、和真核凝缩蛋白。 SMC-kleisin 蛋白复合物的分子动力学模拟表明，这些复合物作为由不同拓扑异构体组成的广泛构象整体而存在。模拟表明 SMC 盘绕线圈区域发挥着关键作用，其中线圈与各种连接数交织在一起。这些编织线圈的扭曲和扭动与 SMC 头域的运动相结合，表明这些复合物可能起到拓扑马达的作用。当 DNA 与编织线圈缠绕时，SMC-kleisin 蛋白复合物沿着 DNA 的打开、关闭和翻译将使这些马达能够耦合到 DNA 的拓扑结构。