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阐明黏连蛋白 ATP 酶结构的机制解开 SMC- kleisin 环。

The structure of the cohesin ATPase elucidates the mechanism of SMC-kleisin ring opening.

机构信息

European Molecular Biology Laboratory, Grenoble, France.

MRC Laboratory of Molecular Biology, Cambridge, UK.

出版信息

Nat Struct Mol Biol. 2020 Mar;27(3):233-239. doi: 10.1038/s41594-020-0379-7. Epub 2020 Feb 17.

DOI:10.1038/s41594-020-0379-7
PMID:32066964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7100847/
Abstract

Genome regulation requires control of chromosome organization by SMC-kleisin complexes. The cohesin complex contains the Smc1 and Smc3 subunits that associate with the kleisin Scc1 to form a ring-shaped complex that can topologically engage chromatin to regulate chromatin structure. Release from chromatin involves opening of the ring at the Smc3-Scc1 interface in a reaction that is controlled by acetylation and engagement of the Smc ATPase head domains. To understand the underlying molecular mechanisms, we have determined the 3.2-Å resolution cryo-electron microscopy structure of the ATPγS-bound, heterotrimeric cohesin ATPase head module and the 2.1-Å resolution crystal structure of a nucleotide-free Smc1-Scc1 subcomplex from Saccharomyces cerevisiae and Chaetomium thermophilium. We found that ATP-binding and Smc1-Smc3 heterodimerization promote conformational changes within the ATPase that are transmitted to the Smc coiled-coil domains. Remodeling of the coiled-coil domain of Smc3 abrogates the binding surface for Scc1, thus leading to ring opening at the Smc3-Scc1 interface.

摘要

基因组调控需要 SMC- kleisin 复合物来控制染色体的组织。黏合蛋白复合物包含 Smc1 和 Smc3 亚基，它们与 kleisin Scc1 结合形成一个环形复合物，可以在拓扑上与染色质结合，从而调节染色质结构。从染色质上释放出来涉及到在 Smc3-Scc1 界面处打开环，该反应受乙酰化和 Smc ATP 酶头部结构域的参与控制。为了理解潜在的分子机制，我们已经确定了 3.2Å 分辨率的 ATPγS 结合的、异三聚体黏合蛋白 ATP 酶头部模块的冷冻电镜结构和来自酿酒酵母和嗜热毛壳菌的核苷酸自由 Smc1-Scc1 亚复合物的 2.1Å 分辨率晶体结构。我们发现，ATP 结合和 Smc1-Smc3 异二聚化促进了 ATP 酶内的构象变化，这些变化被传递到 Smc 卷曲螺旋结构域。Smc3 卷曲螺旋结构域的重塑破坏了 Scc1 的结合表面，从而导致 Smc3-Scc1 界面处的环打开。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/dcb0c6b1e843/EMS85447-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/d21fd0cb36a5/EMS85447-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/393e72e7cac2/EMS85447-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/ec37766041f2/EMS85447-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/84fc6863a405/EMS85447-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/bfac27bd6ddf/EMS85447-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/bf7fba4aa3c8/EMS85447-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/dcb0c6b1e843/EMS85447-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/d21fd0cb36a5/EMS85447-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/393e72e7cac2/EMS85447-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/ec37766041f2/EMS85447-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/84fc6863a405/EMS85447-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/bfac27bd6ddf/EMS85447-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/bf7fba4aa3c8/EMS85447-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a5a/7100847/dcb0c6b1e843/EMS85447-f003.jpg

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