251. The structure of the cohesin ATPase elucidates the mechanism of SMC–kleisin ring opening
- Author
-
Daniel Panne, Yan Li, Kyle W. Muir, and Felix Weis
- Subjects
Models, Molecular ,Protein Conformation, alpha-Helical ,Chromosomal Proteins, Non-Histone ,ATPase ,Gene Expression ,Cell Cycle Proteins ,Plasma protein binding ,Chaetomium ,Crystallography, X-Ray ,genome regulation ,0302 clinical medicine ,Protein structure ,Adenosine Triphosphate ,Structural Biology ,Heterotrimeric G protein ,Cloning, Molecular ,Cohesin ,Adenosine Triphosphatases ,0303 health sciences ,biology ,Chemistry ,SMC ,Recombinant Proteins ,Chromatin ,cryoEM ,Protein Binding ,Saccharomyces cerevisiae Proteins ,Cohesin complex ,Saccharomyces cerevisiae ,Genetic Vectors ,Chromatin folding ,Article ,03 medical and health sciences ,Escherichia coli ,Protein Interaction Domains and Motifs ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,Binding Sites ,Sequence Homology, Amino Acid ,Cryoelectron Microscopy ,biology.organism_classification ,Biophysics ,biology.protein ,Protein Conformation, beta-Strand ,Protein Multimerization ,Sequence Alignment ,030217 neurology & neurosurgery - 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-A resolution cryo-electron microscopy structure of the ATPγS-bound, heterotrimeric cohesin ATPase head module and the 2.1-A 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. Structural analysis reveals that ATP-binding and Smc1–Smc3 heterodimerization promotes conformational changes within the cohesin ATPase that are transmitted to the Smc coiled-coil domains, leading to ring opening at the Smc3–Scc1 interface.
- Published
- 2020