1. Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms.
- Author
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Li Q, Zhang J, Haluska C, Zhang X, Wang L, Liu G, Wang Z, Jin D, Cheng T, Wang H, Tian Y, Wang X, Sun L, Zhao X, Chen Z, and Wang L
- Subjects
- Protein Conformation, Chromosomal Proteins, Non-Histone chemistry, Chromosomal Proteins, Non-Histone metabolism, Chromosomal Proteins, Non-Histone ultrastructure, Cryoelectron Microscopy, Saccharomyces cerevisiae Proteins chemistry, Saccharomyces cerevisiae Proteins metabolism, Saccharomyces cerevisiae Proteins ultrastructure, Cell Cycle Proteins metabolism, Cell Cycle Proteins chemistry, Cell Cycle Proteins ultrastructure, Saccharomyces cerevisiae metabolism, Models, Molecular
- Abstract
Smc5/6 is a member of the eukaryotic structural maintenance of chromosomes (SMC) family of complexes with important roles in genome maintenance and viral restriction. However, limited structural understanding of Smc5/6 hinders the elucidation of its diverse functions. Here, we report cryo-EM structures of the budding yeast Smc5/6 complex in eight-subunit, six-subunit and five-subunit states. Structural maps throughout the entire length of these complexes reveal modularity and key elements in complex assembly. We show that the non-SMC element (Nse)2 subunit supports the overall shape of the complex and uses a wedge motif to aid the stability and function of the complex. The Nse6 subunit features a flexible hook region for attachment to the Smc5 and Smc6 arm regions, contributing to the DNA repair roles of the complex. Our results also suggest a structural basis for the opposite effects of the Nse1-3-4 and Nse5-6 subcomplexes in regulating Smc5/6 ATPase activity. Collectively, our integrated structural and functional data provide a framework for understanding Smc5/6 assembly and function., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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