6CW2

Crystal structure of a yeast SAGA transcriptional coactivator Ada2/Gcn5 HAT subcomplex, crystal form 1

Summary for 6CW2

• Entry DOI: 10.2210/pdb6cw2/pdb
• Descriptor: Histone acetyltransferase GCN5, Transcriptional adapter 2, antibody heavy chain, ... (6 entities in total)
• Functional Keywords: ada2/gcn5 structure, gene regulation
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 4
• Total formula weight: 90969.56

Authors

Sun, J.,Paduch, M.,Kim, S.A.,Kramer, R.M.,Barrios, A.F.,Lu, V.,Luke, J.,Usatyuk, S.,Kossiakoff, A.A.,Tan, S. (deposition date: 2018-03-29, release date: 2018-09-19, Last modification date: 2024-10-23)

Primary citation

Sun, J.,Paduch, M.,Kim, S.A.,Kramer, R.M.,Barrios, A.F.,Lu, V.,Luke, J.,Usatyuk, S.,Kossiakoff, A.A.,Tan, S.
Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2.
Proc. Natl. Acad. Sci. U.S.A., 115:10010-10015, 2018

PubMed 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.

PubMed: 30224453
DOI: 10.1073/pnas.1805343115

Experimental method

X-RAY DIFFRACTION (2.67 Å)