Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms Journal Article
| Authors: | 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.; Wang, L. |
| Article Title: | Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms |
| 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. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. |
| Keywords: | controlled study; unclassified drug; nonhuman; protein conformation; protein function; cohesin; cell cycle protein; nonhistone protein; animal cell; metabolism; cell cycle proteins; chromosomal proteins, non-histone; complex formation; dna repair; protein assembly; protein stability; enzyme activity; chemistry; regulatory mechanism; saccharomyces cerevisiae; gene interaction; binding site; models, molecular; dimerization; conformational transition; saccharomyces cerevisiae proteins; protein subunit; saccharomyces cerevisiae protein; protein structure; sequence homology; x ray crystallography; adenosine triphosphatase; sumo protein; heterodimer; ultrastructure; genetic conservation; stereospecificity; fungal protein; molecular model; diploidy; ligase; cryoelectron microscopy; budding yeast; fission yeast; heterodimerization; recombination repair; article; smc5 protein; smc6 protein; coimmunoprecipitation; hinge region; sf9 cell line; negative staining; nse1 protein; nse3 protein; nse4 protein; structural model; nse5 protein; nse6 protein; smc5 protein, s cerevisiae; smc6 protein, s cerevisiae |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 31 |
| Issue: | 10 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-10-01 |
| Start Page: | 1532 |
| End Page: | 1542 |
| Language: | English |
| DOI: | 10.1038/s41594-024-01319-1 |
| PUBMED: | 38890552 |
| PROVIDER: | scopus |
| PMCID: | PMC11479838 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Xiaolan Zhao -- Source: Scopus |
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