Pobegalov, Georgii;
Chu, Lee-Ya;
Peters, Jan-Michael;
Molodtsov, Maxim I;
(2023)
Single cohesin molecules generate force by two distinct mechanisms.
Nature Communications
, 14
, Article 3946. 10.1038/s41467-023-39696-8.
Preview |
Text
s41467-023-39696-8.pdf - Published Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Single cohesin molecules generate force by two distinct mechanisms |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-023-39696-8 |
| Publisher version: | https://doi.org/10.1038/s41467-023-39696-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10172929 |
Archive Staff Only
 |
View Item |
