7TVE

ATP and DNA bound SMC5/6 core complex

Summary for 7TVE

• Entry DOI: 10.2210/pdb7tve/pdb
• EMDB information: 26140
• Descriptor: DNA (68-MER), DNA (78-MER), Non-structural maintenance of chromosomes element 1, ... (8 entities in total)
• Functional Keywords: nse1, nse3, nse4, smc5, smc6, nse2, atp, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Saccharomyces cerevisiae W303; More
• Total number of polymer chains: 7
• Total formula weight: 423064.83

Authors

Yu, Y.,Patel, D.J. (deposition date: 2022-02-04, release date: 2022-06-22, Last modification date: 2024-02-21)

Primary citation

Yu, Y.,Li, S.,Ser, Z.,Kuang, H.,Than, T.,Guan, D.,Zhao, X.,Patel, D.J.
Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes.
Proc.Natl.Acad.Sci.USA, 119:e2202799119-e2202799119, 2022

PubMed Abstract: Structural maintenance of chromosomes (SMC) complexes are essential for chromatin organization and functions throughout the cell cycle. The cohesin and condensin SMCs fold and tether DNA, while Smc5/6 directly promotes DNA replication and repair. The functions of SMCs rely on their abilities to engage DNA, but how Smc5/6 binds and translocates on DNA remains largely unknown. Here, we present a 3.8 Å cryogenic electron microscopy (cryo-EM) structure of DNA-bound Saccharomyces cerevisiae Smc5/6 complex containing five of its core subunits, including Smc5, Smc6, and the Nse1-3-4 subcomplex. Intricate interactions among these subunits support the formation of a clamp that encircles the DNA double helix. The positively charged inner surface of the clamp contacts DNA in a nonsequence-specific manner involving numerous DNA binding residues from four subunits. The DNA duplex is held up by Smc5 and 6 head regions and positioned between their coiled-coil arm regions, reflecting an engaged-head and open-arm configuration. The Nse3 subunit secures the DNA from above, while the hook-shaped Nse4 kleisin forms a scaffold connecting DNA and all other subunits. The Smc5/6 DNA clamp shares similarities with DNA-clamps formed by other SMCs but also exhibits differences that reflect its unique functions. Mapping cross-linking mass spectrometry data derived from DNA-free Smc5/6 to the DNA-bound Smc5/6 structure identifies multi-subunit conformational changes that enable DNA capture. Finally, mutational data from cells reveal distinct DNA binding contributions from each subunit to Smc5/6 chromatin association and cell fitness. In summary, our integrative study illuminates how a unique SMC complex engages DNA in supporting genome regulation.

PubMed: 35648833
DOI: 10.1073/pnas.2202799119

Experimental method

ELECTRON MICROSCOPY (3.8 Å)