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

Sun, Jian; Paduch, Marcin; Kim, Sang-Ah; Kramer, Ryan M.; Barrios, Adam F.; Lu, Vincent; Luke, Judy; Usatyuk, Svitlana; Kossiakoff, Anthony A.; Tan, Song

doi:10.1073/pnas.1805343115

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

Journal Article · Mon Sep 17 00:00:00 EDT 2018 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1805343115· OSTI ID:1477118

Sun, Jian ^[1]; Paduch, Marcin ^[2]; Kim, Sang-Ah ^[1]; Kramer, Ryan M. ^[3]; Barrios, Adam F. ^[4]; Lu, Vincent ^[5]; Luke, Judy ^[5]; Usatyuk, Svitlana ^[5]; Kossiakoff, Anthony A. ^[5]; Tan, Song ^[1]

Pennsylvania State Univ., University Park, PA (United States)
Univ. of Chicago, IL (United States); Grail, Menlo Park, CA (United States)
Pennsylvania State Univ., University Park, PA (United States); Air Force Research Lab., Wright Patterson AFB, OH (United States)
Pennsylvania State Univ., University Park, PA (United States); DesigneRx Pharmaceuticals, Vacaville, CA (United States)
Univ. of Chicago, IL (United States)

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. As a result, this finding suggests a mechanism for regulating chromatin modification enzyme activity: controlling binding of the modification cosubstrate instead of the histone substrate.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Inst. of Health

Grant/Contract Number:: R01GM088236; R01GM111651; U01GM094588; R01GM072688; U54HG006436

OSTI ID:: 1477118

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, Issue 40; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 35 works

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59 BASIC BIOLOGICAL SCIENCES
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Title: Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2

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