The structure of the cohesin ATPase elucidates the mechanism of SMC-kleisin ring opening.

Abstract

Genome regulation requires control of chromosomal organization by SMC–kleisin complexes. The cohesin complex contains the Smc1 and Smc3 subunits which 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 cryo-EM structure of the ATPγS-bound, hetero-trimeric cohesin ATPase head module, and the 2.1 Å 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 which 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.