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Single cohesin molecules generate force by two distinct mechanisms

Author

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  • Georgii Pobegalov

    (The Francis Crick Institute
    University College London)

  • Lee-Ya Chu

    (The Francis Crick Institute)

  • Jan-Michael Peters

    (Vienna BioCenter)

  • Maxim I. Molodtsov

    (The Francis Crick Institute
    University College London
    Vienna BioCenter)

Abstract

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.

Suggested Citation

  • Georgii Pobegalov & Lee-Ya Chu & Jan-Michael Peters & Maxim I. Molodtsov, 2023. "Single cohesin molecules generate force by two distinct mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39696-8
    DOI: 10.1038/s41467-023-39696-8
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    References listed on IDEAS

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