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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 10010-10015 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 115 |
| Issue number | 40 |
| DOIs | |
| State | Published - Oct 2 2018 |
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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.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 40, 02.10.2018, p. 10010-10015.Research output: Contribution to journal › Article
TY - JOUR
T1 - Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2
AU - Sun, Jian
AU - Paduch, Marcin
AU - Kim, Sang Ah
AU - Kramer, Ryan M.
AU - Barrios, Adam F.
AU - Lu, Vincent
AU - Luke, Judy
AU - Usatyuk, Svitlana
AU - Kossiakoff, Anthony A.
AU - Tan, Song
PY - 2018/10/2
Y1 - 2018/10/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85054379461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054379461&partnerID=8YFLogxK
U2 - 10.1073/pnas.1805343115
DO - 10.1073/pnas.1805343115
M3 - Article
C2 - 30224453
AN - SCOPUS:85054379461
VL - 115
SP - 10010
EP - 10015
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 40
ER -