1PUA

Crystal Structure of Tetrahymena GCN5 with Bound Coenzyme A and a Phosphorylated, 19-residue Histone H3 peptide

Summary for 1PUA

• Entry DOI: 10.2210/pdb1pua/pdb
• Related: 1M1D 1PU9 1QSN 1QSR 1QST
• Descriptor: HAT A1, Histone H3, COENZYME A, ... (4 entities in total)
• Functional Keywords: histone acetyltransferase, gcn5-related n-acetyltransferase, coa-binding protein, ternary complex, transferase-structural protein complex, transferase/structural protein
• Biological source: Tetrahymena thermophila; More
• Total number of polymer chains: 2
• Total formula weight: 22324.52

Authors

Clements, A.,Poux, A.N.,Lo, W.S.,Pillus, L.,Berger, S.L.,Marmorstein, R. (deposition date: 2003-06-24, release date: 2003-09-23, Last modification date: 2024-10-16)

Primary citation

Clements, A.,Poux, A.N.,Lo, W.S.,Pillus, L.,Berger, S.L.,Marmorstein, R.
Structural basis for histone and phospho-histone binding by the GCN5 histone acetyltransferase
Mol.Cell, 12:461-473, 2003

PubMed Abstract: Distinct posttranslational modifications on histones occur in specific patterns to mediate certain chromosomal events. For example, on histone H3, phosphorylation at Ser10 can enhance GCN5-mediated Lys14 acetylation to promote transcription. To gain insight into the mechanism underlying this synergism, we determined the structure of Tetrahymena GCN5 (tGCN5) and coenzyme A (CoA) bound to unmodified and Ser10-phosphorylated 19 residue histone H3 peptides (H3p19 and H3p19Pi, respectively). The tGCN5/CoA/H3p19 structure reveals that a 12 amino acid core sequence mediates extensive contacts with the protein, providing the structural basis for substrate specificity by the GCN5/PCAF family of histone acetyltransferases. Comparison with the tGCN5/CoA/H3p19Pi structure reveals that phospho-Ser10 and Thr11 mediate significant histone-protein interactions, and nucleate additional interactions distal to the phosphorylation site. Functional studies show that histone H3 Thr11 is necessary for optimal transcription at yGcn5-dependent promoters requiring Ser10 phosphorylation. Together, these studies reveal how one histone modification can modulate another to affect distinct transcriptional signals.

PubMed: 14536085
DOI: 10.1016/S1097-2765(03)00288-0

Experimental method

X-RAY DIFFRACTION (2.3 Å)