Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):10010-10015. doi: 10.1073/pnas.1805343115. Epub 2018 Sep 17.

Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2.

Author information

1
Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802.
2
Department of Biochemistry and Molecular Biology, The University of Chicago, IL 60637.
3
Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802; sxt30@psu.edu.

Abstract

The Gcn5 histone acetyltransferase (HAT) subunit of the SAGA transcriptional coactivator complex catalyzes acetylation of histone H3 and H2B N-terminal tails, posttranslational modifications associated with gene activation. Binding of the SAGA subunit partner Ada2 to Gcn5 activates Gcn5's intrinsically weak HAT activity on histone proteins, but the mechanism for this activation by the Ada2 SANT domain has remained elusive. We have employed Fab antibody fragments as crystallization chaperones to determine crystal structures of a yeast Ada2/Gcn5 complex. Our structural and biochemical results indicate that the Ada2 SANT domain does not activate Gcn5's activity by directly affecting histone peptide binding as previously proposed. Instead, the Ada2 SANT domain enhances Gcn5 binding of the enzymatic cosubstrate acetyl-CoA. This finding suggests a mechanism for regulating chromatin modification enzyme activity: controlling binding of the modification cosubstrate instead of the histone substrate.

KEYWORDS:

X-ray crystallography; chromatin biology; epigenetics; histone modification

PMID:
30224453
PMCID:
PMC6176591
DOI:
10.1073/pnas.1805343115
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center