@article{6f0699a5427747bfa91cdd8282da807d,
title = "Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2",
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.",
author = "Jian Sun and Marcin Paduch and Kim, {Sang Ah} and Kramer, {Ryan M.} and Barrios, {Adam F.} and Vincent Lu and Judy Luke and Svitlana Usatyuk and Kossiakoff, {Anthony A.} and Song Tan",
note = "Funding Information: ACKNOWLEDGMENTS. We are very grateful to the staff of APS NE-CAT beamlines 24-ID-C and 24-ID-E for their help during synchrotron data collection, J. Fecko and N. Yennawar (Penn State Huck Institute X-ray core facility) for assistance with isothermal calorimetry and crystallographic refinement, and members of the laboratory of S.T., Phil Bevilacqua, and the Penn State Center for Eukaryotic Gene Regulation for discussions. This work was supported by National Institutes of Health National Institute of General Medical Sciences Grants R01GM088236 (to S.T.), R01GM111651 (to S.T.), U01GM094588 (to A.A.K.), R01GM072688 (to A.A.K.), and U54HG006436 (to A.A.K.). Funding Information: This work was supported by National Institutes of Health, National Institute of General Medical Sciences Grants R01GM088236 (to S.T.), R01GM111651 (to S.T.), U01GM094588 (to A.A.K.), R01GM072688 (to A.A.K.), and U54HG006436 (to A.A.K.). Publisher Copyright: {\textcopyright} 2018 National Academy of Sciences. All rights reserved.",
year = "2018",
month = oct,
day = "2",
doi = "10.1073/pnas.1805343115",
language = "English (US)",
volume = "115",
pages = "10010--10015",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "40",
}