Nucleosome flipping drives kinetic proofreading and processivity by SWR1.

Autor: Girvan P; Section of Structural Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.; Single Molecule Biophysics Group, MRC Laboratory of Medical Sciences, London, UK., Jalal ASB; Section of Structural Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK., McCormack EA; Section of Structural Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK., Skehan MT; Section of Structural Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK., Knight CL; Section of Structural Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK., Wigley DB; Section of Structural Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK. d.wigley@imperial.ac.uk., Rueda DS; Single Molecule Biophysics Group, MRC Laboratory of Medical Sciences, London, UK. david.rueda@imperial.ac.uk.; Section of Virology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK. david.rueda@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Dec; Vol. 636 (8041), pp. 251-257. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1038/s41586-024-08152-y
Abstrakt: The yeast SWR1 complex catalyses the exchange of histone H2A-H2B dimers in nucleosomes, with Htz1-H2B dimers 1-3 . Here we used single-molecule analysis to demonstrate two-step double exchange of the two H2A-H2B dimers in a canonical yeast nucleosome with Htz1-H2B dimers, and showed that double exchange can be processive without release of the nucleosome from the SWR1 complex. Further analysis showed that bound nucleosomes flip between two states, with each presenting a different face, and hence histone dimer, to SWR1. The bound dwell time is longer when an H2A-H2B dimer is presented for exchange than when presented with an Htz1-H2B dimer. A hexasome intermediate in the reaction is bound to the SWR1 complex in a single orientation with the 'empty' site presented for dimer insertion. Cryo-electron microscopy analysis revealed different populations of complexes showing nucleosomes caught 'flipping' between different conformations without release, each placing a different dimer into position for exchange, with the Swc2 subunit having a key role in this process. Together, the data reveal a processive mechanism for double dimer exchange that explains how SWR1 can 'proofread' the dimer identities within nucleosomes.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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