Single cohesin molecules generate force by two distinct mechanisms

• Published in: Nature communications 2023-07, Vol.14 (1), p.3946-3946, Article 3946
• Main Authors: Pobegalov, Georgii, Chu, Lee-Ya, Peters, Jan-Michael, Molodtsov, Maxim I.
• Format: Article
• Language: English
• Subjects: 101/62; 631/337/100/101; 631/337/2265; 639/766/747; Adenosine Triphosphatases - metabolism; ATP; Cell Cycle Proteins - metabolism; Chromosomal Proteins, Non-Histone - metabolism; Cohesin; Cohesins; Cohesion; Coils; Deoxyribonucleic acid; DNA; Fluctuations; Head movement; Humanities and Social Sciences; Molecular dynamics; Molecular machines; multidisciplinary; Proteins; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-39696-8

Spatial organization of DNA is facilitated by cohesin protein complexes that move on DNA and extrude DNA loops. How cohesin works mechanistically as a molecular machine is poorly understood. Here, we measure mechanical forces generated by conformational changes in single cohesin molecules. We show that bending of SMC coiled coils is driven by random thermal fluctuations leading to a ~32 nm head-hinge displacement that resists forces up to 1 pN; ATPase head engagement occurs in a single step of ~10 nm and is driven by an ATP dependent head-head movement, resisting forces up to 15 pN. Our molecular dynamic simulations show that the energy of head engagement can be stored in a mechanically strained conformation of NIPBL and released during disengagement. These findings reveal how single cohesin molecules generate force by two distinct mechanisms. We present a model, which proposes how this ability may power different aspects of cohesin-DNA interaction. Cohesin protein complex is a molecular machine that extrudes DNA loops. Here, authors show that bending of the molecule’s long coiled coils is driven by thermal fluctuations and engagement of ATPase domains uses ATP energy to generate strong force.