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

FEBS Lett. 2013 Aug 19;587(16):2506-11. doi: 10.1016/j.febslet.2013.06.051. Epub 2013 Jul 4.

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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Histones / chemistry
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Peptides / chemistry
  • Protein Binding
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Zinc / chemistry
  • Zinc Fingers*
  • p300-CBP Transcription Factors / chemistry*

Substances

  • Histones
  • Peptides
  • p300-CBP Transcription Factors
  • Zinc