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.
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.
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