Abstract
Structural maintenance of chromosomes (SMC)-kleisin complexes organize chromosomal DNAs in all domains of life, with key roles in chromosome segregation, DNA repair and regulation of gene expression. They function through the entrapment and active translocation of DNA, but the underlying conformational changes are largely unclear. Using structural biology, mass spectrometry and cross-linking, we investigated the architecture of two evolutionarily distant SMC-kleisin complexes: MukBEF from Escherichia coli, and cohesin from Saccharomyces cerevisiae. We show that both contain a dynamic coiled-coil discontinuity, the elbow, near the middle of their arms that permits a folded conformation. Bending at the elbow brings into proximity the hinge dimerization domain and the head-kleisin module, situated at opposite ends of the arms. Our findings favour SMC activity models that include a large conformational change in the arms, such as a relative movement between DNA contact sites during DNA loading and translocation
| Original language | English |
|---|---|
| Pages (from-to) | 227-236 |
| Number of pages | 10 |
| Journal | Nature Structural & Molecular Biology |
| Volume | 26 |
| DOIs | |
| Publication status | Published - 4 Mar 2019 |
| Externally published | Yes |
Bibliographical note
Acknowledgements: We are grateful to D. Kureisaite-Ciziene for help with crystallography and M. Yu for help with X-ray data collection. We thank X. Deng, F. Coscia and G. Cannone for help with electron microscopy. We thank J. Fredens for advice on recombineering and gift of the pheS*-hygR cassette. We thank G. Fisher and D. Sherratt for help with initial complementation experiments and gift of the neoR marker. We thank S. Gruber and A. Durand for comments on the manuscript. F.B. is funded by an EMBO Long-Term Fellowship (EMBO ALTF 1151-2017). This work was funded by the Medical Research Council (U105184326 to J.L.), the Wellcome Trust (202754/Z/16/Z to J.L.), the DFG (25065445 to J.R.), and the Wellcome Trust through a Senior Research Fellowship to J.R. (103139). The Wellcome Centre for Cell Biology is supported by core funding from the Wellcome Trust (203149).Funding
Cancer Research UK
Grant ID: 26747:
Establishment of sister chromatid cohesion by cohesin Grant ID: 12386
Medical Research Council:
The control of chromosome structure by cohesin/condensin complexes, Grant ID: G0401545
Molecular machines - the bacterial cytoskeleton, Grant ID: MC_U105184326
Wellcome Trust
Actin-like cytoskeletal systems in bacteria and archaea, Grant ID: 02754/Z/16/Z Protein structures in the context of time and space by mass spectrometry. Grant ID: 103139/Z/13/Z
Core Funding for the Wellcome Trust Centre for Cell Biology, Grant ID: 203149
