The HP1 chromo shadow domain binds a consensus peptide pentamer

Curr Biol. 2000 Jan 13;10(1):27-30. doi: 10.1016/s0960-9822(99)00260-2.

Abstract

Heterochromatin-associated protein 1 (HP1) is thought to affect chromatin structure through interactions with other proteins in heterochromatin. Chromo domains located near the amino (amino chromo) and carboxy (chromo shadow) termini of HP1 may mediate such interactions, as suggested by domain swapping, in vitro binding and 3D structural studies . Several HP1-associated proteins have been reported, providing candidates that might specifically complex with the chromo domains of HP1. However, such association studies provide little mechanistic insight and explore only a limited set of potential interactions in a largely non-competitive setting. To determine how chromo domains can selectively interact with other proteins, we probed random peptide phage display libraries using chromo domains from HP1. Our results demonstrate that a consensus pentapeptide is suffident for specific interaction with the HP1 chromo shadow domain. The pentapeptide is found in the amino acid sequence of reported HP1-associated proteins, including the shadow domain itself. Peptides that bind the shadow domain also disrupt shadow domain dimers. Our results suggest that HP1 dimerization, which is thought to mediate heterochromatin compaction and cohesion, occurs via pentapeptide binding. In general, chromo domains may function by avidly binding short peptides at the surface of chromatin-associated proteins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Consensus Sequence
  • Dimerization
  • Drosophila melanogaster / metabolism
  • Heterochromatin / metabolism
  • Humans
  • Insect Proteins / chemistry
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Peptide Library
  • Protein Conformation
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Insect Proteins
  • Peptide Fragments
  • Peptide Library
  • heterochromatin-specific nonhistone chromosomal protein HP-1