Cryo-EM structure of the human Sirtuin 6-nucleosome complex [preprint]
AuthorsChio, Un Seng
Bryll, Alysia R
Feldman, Jessica L
Peterson, Craig L
Student AuthorsAlysia Bryll
UMass Chan AffiliationsMorningside Graduate School of Biomedical Sciences
Program in Molecular Medicine
T.H. Chan School of Medicine
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AbstractSirtuin 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.
SourceChio 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.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52129
NotesThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
Related ResourcesNow published in Science Advances doi: 10.1126/sciadv.adf7586
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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