Structure of Full-Length SMC and Rearrangements Required for Chromosome Organization

• Published in: Molecular cell Vol. 67; no. 2; pp. 334 - 347.e5
• Main Authors: Diebold-Durand, Marie-Laure, Lee, Hansol, Ruiz Avila, Laura B., Noh, Haemin, Shin, Ho-Chul, Im, Haeri, Bock, Florian P., Bürmann, Frank, Durand, Alexandre, Basfeld, Alrun, Ham, Sihyun, Basquin, Jérôme, Oh, Byung-Ha, Gruber, Stephan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-07-2017; Cell Press
• Subjects: Adenosine Triphosphate - metabolism; Bacillus subtilis - genetics; Bacillus subtilis - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding Sites; Biochemistry, Molecular Biology; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; chromosome condensation; Chromosome Segregation; Chromosomes, Bacterial; cohesion; condensin; Crystallography, X-Ray; Cysteine; DNA loop extrusion; High-Throughput Screening Assays; kite; kleisin; Life Sciences; Models, Molecular; MukB; Mutation; Nucleic Acid Conformation; Protein Conformation; Protein Multimerization; Protein Stability; Rad50; ScpA; ScpB; SMC; Structure-Activity Relationship; Rad50; condensin; kleisin; ScpB; ScpA; SMC; cohesion; MukB; chromosome condensation; DNA loop extrusion; kite
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2017.06.010

Multi-subunit SMC complexes control chromosome superstructure and promote chromosome disjunction, conceivably by actively translocating along DNA double helices. SMC subunits comprise an ABC ATPase “head” and a “hinge” dimerization domain connected by a 49 nm coiled-coil “arm.” The heads undergo ATP-dependent engagement and disengagement to drive SMC action on the chromosome. Here, we elucidate the architecture of prokaryotic Smc dimers by high-throughput cysteine cross-linking and crystallography. Co-alignment of the Smc arms tightly closes the interarm space and misaligns the Smc head domains at the end of the rod by close apposition of their ABC signature motifs. Sandwiching of ATP molecules between Smc heads requires them to substantially tilt and translate relative to each other, thereby opening up the Smc arms. We show that this mechanochemical gating reaction regulates chromosome targeting and propose a mechanism for DNA translocation based on the merging of DNA loops upon closure of Smc arms.
[Display omitted]
•Crystallography and in vivo cross-linking reveal the architecture of prokaryotic Smc•Juxtaposition of the Smc arms misaligns the two Smc ATPase domains•Smc head engagement mechanically opens an interarm space•A model for DNA loop extrusion driven by the SMC ATPase cycle is presented
By combining high-throughput in vivo cysteine cross-linking and crystallography, Diebold-Durand et al. construct a high-resolution model of full-length prokaryotic Smc. It reveals that the rod-shaped Smc dimer lacks chambers for DNA and features misaligned head domains. Smc head engagement mechanically opens an interarm space.