The CH2 domain of CBP/p300 is a novel zinc finger

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 brornodomain 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. Structured summary of protein interactions: H4 binds to CBP by peptide array (View Interaction: 1, 2). (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.