Molecular Basis for SMC Rod Formation and Its Dissolution upon DNA Binding

Abstract

SummarySMC condensin complexes are central modulators of chromosome superstructure in all branches of life. Their SMC subunits form a long intramolecular coiled coil, which connects a constitutive “hinge” dimerization domain with an ATP-regulated “head” dimerization module. Here, we address the structural arrangement of the long coiled coils in SMC complexes. We unequivocally show that prokaryotic Smc-ScpAB, eukaryotic condensin, and possibly also cohesin form rod-like structures, with their coiled coils being closely juxtaposed and accurately anchored to the hinge. Upon ATP-induced binding of DNA to the hinge, however, Smc switches to a more open configuration. Our data suggest that a long-distance structural transition is transmitted from the Smc head domains to regulate Smc-ScpAB’s association with DNA. These findings uncover a conserved architectural theme in SMC complexes, provide a mechanistic basis for Smc’s dynamic engagement with chromosomes, and offer a molecular explanation for defects in Cornelia de Lange syndrome.

Structural Basis for Dimer Formation of Human Condensin Structural Maintenance of Chromosome Proteins and Its Implications for Single-stranded DNA Recognition

“…1), to the corresponding aspartate residues, disrupting the dimerization of the SMC (1,8). Taking this into consideration, Gly 3 Asp mutations were introduced into the corresponding regions of hSmc2H-CC30 (hSmc2H(G/D)-CC30); they were analyzed by sedimentation velocity AUC experiments (Fig.…”

“…These structures revealed that the eukaryotic Smc hinges form similar folds as the prokaryotic and bacterial Smc hinge domains, demonstrating that the overall structure of the Smc hinge domain is universal for a wide variety of SMC and SMC-like proteins. Under these circumstances, very recently Soh et al (1) reported a SMC rod formation based on the crystal structures of the Pyrococcus furiosus Smc hinge (Pf SmcH) with long coiled coils and the yeast Smc2-4 hinge (ScSmc2-4H) with long coiled coils. This study paves the way for understanding structural difference of condensin and cohesin hinge region and for clarifying precise molecular machinery of chromosome structural alternations by bacterial Smc and cohesin.…”

The Blueprint of a Minimal Cell: MiniBacillus

“…After the initiation of DNA replication, the newly formed origin regions are bound and separated by the condensin protein complex. The condensin complex is composed of two subunits of the Smc protein and monomers of ScpA and ScpB (51,52). The essential topoisomerase IV formed by ParC and ParE is required for both DNA condensation and segregation (53).…”

The torments of the cohesin ring

“…ATP-dependent head engagement promotes dissolution of the Bacillus subtilis Smc rod and is antagonized by the hinge dimerization. 16,17 Changes in the degree of ring supercoiling might be the means to transmit the conformational change from the heads to the hinge and force the hinge to open. The cohesin loader protein Scc2, which makes contacts with the Smc arms and with other regions of cohesin, 18-21 might also be involved in this process (Fig.…”

“…16,[24][25][26] Thus, it is likely that all protein complexes containing Smc-like subunits are able to transition between the "arms together" and "arms apart" forms and this transition is important for their function. The long-range allosteric regulation involving coiled coils was studied in the cohesin-related Rad50/Mre11 complex which tethers the ends of broken DNA molecules to facilitate DNA repair.…”