Cryo-EM structure of the human Sirtuin 6-nucleosome complex [preprint]
Authors
Chio, Un SengRechiche, Othman
Bryll, Alysia R
Zhu, Jiang
Feldman, Jessica L
Peterson, Craig L
Tan, Song
Armache, Jean-Paul
Student Authors
Alysia BryllAcademic Program
MD/PhDUMass Chan Affiliations
Morningside Graduate School of Biomedical SciencesProgram in Molecular Medicine
T.H. Chan School of Medicine
Document Type
PreprintPublication Date
2023-03-18
Metadata
Show full item recordAbstract
Sirtuin 6 (SIRT6) is a multifaceted protein deacetylase/deacylase and a major target for small-molecule modulators of longevity and cancer. In the context of chromatin, SIRT6 removes acetyl groups from histone H3 in nucleosomes, but the molecular basis for its nucleosomal substrate preference is unknown. Our cryo-electron microscopy structure of human SIRT6 in complex with the nucleosome shows that the catalytic domain of SIRT6 pries DNA from the nucleosomal entry-exit site and exposes the histone H3 N-terminal helix, while the SIRT6 zinc-binding domain binds to the histone acidic patch using an arginine anchor. In addition, SIRT6 forms an inhibitory interaction with the C-terminal tail of histone H2A. The structure provides insights into how SIRT6 can deacetylate both H3 K9 and H3 K56. Teaser: The structure of the SIRT6 deacetylase/nucleosome complex suggests how the enzyme acts on both histone H3 K9 and K56 residues.Source
Chio US, Rechiche O, Bryll AR, Zhu J, Feldman JL, Peterson CL, Tan S, Armache JP. Cryo-EM structure of the human Sirtuin 6-nucleosome complex. bioRxiv [Preprint]. 2023 Mar 18:2023.03.17.533206. doi: 10.1101/2023.03.17.533206. Update in: Sci Adv. 2023 Apr 14;9(15):eadf7586. PMID: 36993468; PMCID: PMC10055229.DOI
10.1101/2023.03.17.533206Permanent Link to this Item
http://hdl.handle.net/20.500.14038/52129PubMed ID
36993468Notes
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Related Resources
Now published in Science Advances doi: 10.1126/sciadv.adf7586Rights
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.; Attribution-NonCommercial-NoDerivatives 4.0 InternationalDistribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/2023.03.17.533206
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.; Attribution-NonCommercial-NoDerivatives 4.0 International