8g57
From Proteopedia
Structure of nucleosome-bound Sirtuin 6 deacetylase
Structural highlights
FunctionSIR6_HUMAN NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.[1] [2] [3] [4] [5] Publication Abstract from PubMedSirtuin 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. Cryo-EM structure of the human Sirtuin 6-nucleosome complex.,Chio US, Rechiche O, Bryll AR, Zhu J, Leith EM, Feldman JL, Peterson CL, Tan S, Armache JP Sci Adv. 2023 Apr 14;9(15):eadf7586. doi: 10.1126/sciadv.adf7586. Epub 2023 Apr , 14. PMID:37058572[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
Categories: Homo sapiens | Large Structures | Synthetic construct | Xenopus laevis | Armache J-P | Bryll AR | Chio US | Feldman JL | Peterson CL | Rechiche O | Tan S | Zhu J
