cohesin_head_DP.pdf (4.24 MB)
The structure of the cohesin ATPase elucidates the mechanism of SMC–kleisin ring opening
journal contribution
posted on 2020-04-01, 08:50 authored by Kyle W. Muir, Yan Li, Felix Weis, Daniel PanneGenome 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.
History
Citation
Nat Struct Mol Biol 27, 233–239 (2020). https://doi.org/10.1038/s41594-020-0379-7Author affiliation
Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell BiologyVersion
- AM (Accepted Manuscript)