Cryo-EM structures of holo condensin reveal a subunit flip-flop mechanism

DOI: 10.1038/s41594-020-0457-x

Authors: Byung-gil Lee (MRC Laboratory of Molecular Biology) , Fabian Merkel (European Molecular Biology Laboratory (EMBL)) , Matteo Allegretti (European Molecular Biology Laboratory (EMBL)) , Markus Hassler (European Molecular Biology Laboratory (EMBL); Julius-Maximilians-Universität Würzburg) , Christopher Cawood (MRC London Institute of Medical Sciences) , Léa Lecomte (European Molecular Biology Laboratory (EMBL)) , Francis J. O'reilly (Technische Universität Berlin) , Ludwig R. Sinn (Technische Universität Berlin) , Pilar Gutierrez-escribano (MRC London Institute of Medical Sciences) , Marc Kschonsak (European Molecular Biology Laboratory (EMBL)) , Sol Bravo (European Molecular Biology Laboratory (EMBL)) , Takanori Nakane (MRC Laboratory of Molecular Biology) , Juri Rappsilber (Technische Universität Berlin; University of Edinburgh) , Luis Aragon (MRC London Institute of Medical Sciences) , Martin Beck (European Molecular Biology Laboratory (EMBL); Max Planck Institute of Biophysics) , Jan Lowe (MRC Laboratory of Molecular Biology) , Christian H. Haering (European Molecular Biology Laboratory (EMBL); Julius-Maximilians-Universität Würzburg)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 53

State: Published (Approved)
Published: July 2020

Abstract: Complexes containing a pair of structural maintenance of chromosomes (SMC) family proteins are fundamental for the three-dimensional (3D) organization of genomes in all domains of life. The eukaryotic SMC complexes cohesin and condensin are thought to fold interphase and mitotic chromosomes, respectively, into large loop domains, although the underlying molecular mechanisms have remained unknown. We used cryo-EM to investigate the nucleotide-driven reaction cycle of condensin from the budding yeast Saccharomyces cerevisiae. Our structures of the five-subunit condensin holo complex at different functional stages suggest that ATP binding induces the transition of the SMC coiled coils from a folded-rod conformation into a more open architecture. ATP binding simultaneously triggers the exchange of the two HEAT-repeat subunits bound to the SMC ATPase head domains. We propose that these steps result in the interconversion of DNA-binding sites in the catalytic core of condensin, forming the basis of the DNA translocation and loop-extrusion activities.

Journal Keywords: Chromosomes; Cryoelectron microscopy

Subject Areas: Biology and Bio-materials

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