title: The CH2 domain of CBP/p300 is a novel zinc finger.
abstract: The transcriptional co-regulator CBP (CREB-binding protein) has a highly conserved cysteine/histidine-rich region (CH2) whose structure and function remain uncharacterized. Using nuclear magnetic resonance (NMR spectroscopy), sequence alignment, mass spectrometry, and mutagenesis, we show that the CH2 domain is not a canonical plant homeodomain (PHD) finger, as previously proposed, but binds an additional zinc atom through the region N-terminal to the putative PHD motif. The CH2 domain and the preceding bromodomain interact and mutually stabilize each other, implying a cooperative function. We tested the hypothesis that the bromodomain and the CH2 domain can interact with histones, but found that the CH2 does not participate in histone-recognition.
authors.affiliation: Department of Integrative Structural and Computational Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Sangho
authors.initials: S
authors.lastname: Park
authors.forename: Maria A
authors.initials: MA
authors.lastname: Martinez-Yamout
authors.forename: H Jane
authors.initials: HJ
authors.lastname: Dyson
authors.forename: Peter E
authors.initials: PE
authors.lastname: Wright
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006657:Histones / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers; D050880:p300-CBP Transcription Factors / Q000737:chemistry*
chemical_list: D006657:Histones; D010455:Peptides; D050880:p300-CBP Transcription Factors; D015032:Zinc
keywords: BRD; Bromodomain; CBP; CD; CH2; CREB-binding protein; HAT; HSQC; NMR; PHD; Plant homeodomain; Zinc finger; bromodomain; circular dichroism; cysteine/histidine-rich region 2; heteronuclear single-quantum coherence; histone acetyl transferase; nuclear magnetic resonance; p300; plant homeodomain