6cw3 | pdb_00006cw3
Crystal structure of a yeast SAGA transcriptional coactivator Ada2/Gcn5 HAT subcomplex, crystal form 2
Structural highlights
FunctionGCN5_YEAST Acetylates histone H2B to form H2BK11ac and H2BK16ac, histone H3 to form H3K9ac, H3K14ac, H3K18ac, H3K23ac, H3K27ac and H3K36ac, with a lower preference histone H4 to form H4K8ac and H4K16ac, and contributes to H2A.Z acetylation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Operates in concert with certain DNA-binding transcriptional activators such as GCN4 or HAP2/3/4. Its acetyltransferase activity seems to be dependent on the association in different multisubunit complexes. Functions as histone acetyltransferase component of the transcription regulatory histone acetylation (HAT) complexes SAGA, SALSA and ADA. SAGA is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SALSA, an altered form of SAGA, may be involved in positive transcriptional regulation. The ADA histone acetyltransferase complex preferentially acetylates nucleosomal histones H3 (to form H3K14ac and H3K18ac) and H2B, leading to transcription regulation. SLIK is proposed to have partly overlapping functions with SAGA. It preferentially acetylates methylated histone H3, at least after activation at the GAL1-10 locus.[1] [2] [3] Publication Abstract from PubMedThe 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. Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2.,Sun J, Paduch M, Kim SA, Kramer RM, Barrios AF, Lu V, Luke J, Usatyuk S, Kossiakoff AA, Tan S Proc Natl Acad Sci U S A. 2018 Sep 17. pii: 1805343115. doi:, 10.1073/pnas.1805343115. PMID:30224453[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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