Braiding topology and the energy landscape of chromosome organization proteins
Braiding topology and the energy landscape of chromosome organization proteins
复制标题
DOI：
10.1073/pnas.1917750117
复制
发表时间：
2020-01-21
影响因子：
11.1
通讯作者：
Onuchic, Jose N.
中科院分区：
文献类型：
--
作者：
Krepel, Dana;Davtyan, Aram;Onuchic, Jose N.
染色体结构维持(SMC)蛋白和Kleisin亚基的组装对染色体的组织和所有生命王国的分离都是必不可少的。虽然SMC-kleisin复合体的部分结构数据已经存在，但整个复合体的完整结构尚未确定，这使得机理研究变得困难。使用一种结合了关于球状亚域的结晶学结构信息、共同进化信息和能量景观优化力场(AWSEM)的综合方法，我们预测了几个三方SMC-kleisin复合体的原子级结构，包括原核凝聚素、真核凝集素和真核凝聚素。对SMC-Kleisin蛋白质复合体的分子动力学模拟表明，这些复合体是由不同的拓扑异构体组成的广泛的构象系综。模拟表明，SMC线圈区域扮演着关键角色，在该区域中，线圈与不同的连接数交织在一起。这些编织线圈的扭曲和扭曲与SMC头域的运动相耦合，表明该复合体可能起到拓扑马达的作用。SMC-kleisin蛋白复合体的打开、关闭和沿DNA的平移将使这些马达在DNA与编织线圈缠绕时耦合到DNA的拓扑结构。
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.