The cohesin ATPase cycle is mediated by specific conformational dynamics and interface plasticity of SMC1A and SMC3 ATPase domains
Cohesin is key to eukaryotic genome organization and acts throughout the cell cycle in an ATP-dependent manner. The mechanisms underlying cohesin ATPase activity are poorly understood. Here, we characterize distinct steps of the human cohesin ATPase cycle and show that the SMC1A and SMC3 ATPase domains undergo specific but concerted structural rearrangements along this cycle. Specifically, whereas the proximal coiled coil of the SMC1A ATPase domain remains conformationally stable, that of the SMC3 displays an intrinsic flexibility. The ATP-dependent formation of the heterodimeric SMC1A/SMC3 ATPase module (engaged state) favors this flexibility, which is counteracted by NIPBL and DNA binding (clamped state). Opening of the SMC3/RAD21 interface (open-engaged state) stiffens the SMC3 proximal coiled coil, thus constricting together with that of SMC1A the ATPase module DNA-binding chamber. The plasticity of the ATP-dependent interface between the SMC1A and SMC3 ATPase domains enables these structural rearrangements while keeping the ATP gate shut. VIDEO ABSTRACT.
Authors
- Christelle Golzio (ORCID: https://orcid.org/0000-0002-4420-3921)
- T.B. Shaik (ORCID: https://orcid.org/0000-0001-6983-7966)
- Karl Brillet (ORCID: https://orcid.org/0000-0002-7900-8923)
- C. R. Weber (ORCID: https://orcid.org/0009-0008-8935-3350)
- A. Durand (ORCID: https://orcid.org/0000-0002-9173-6886)
- Erwan Watrin (ORCID: https://orcid.org/0000-0002-4582-6493)
- Eric Ennifar (ORCID: https://orcid.org/0000-0002-5076-846X)
- Edouard Troesch
- Ludivine Dulac
- Marie-Laure Diebold (ORCID: https://orcid.org/0000-0002-2061-9260)
- Christophe Romier (ORCID: https://orcid.org/0000-0002-3680-935X)
- Pauline Landwerlin
- Christophe Decroos (ORCID: https://orcid.org/0000-0002-2610-3484)
- Marianne Victoria Lemée
- Pierre Antony
- Marina Vitoria Gomes
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Institut de génétique et de développement de Rennes (FR)
- Architecture et Réactivité de l'arN (FR)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114656
- Citations
- 4
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.30
Funders
- Association pour la Recherche sur le Cancer
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Université de Strasbourg
- Centre National de la Recherche Scientifique
- French Infrastructure for Integrated Structural Biology