Dimerisation of a Chromo Shadow Domain and Distinctions From the Chromodomain as Revealed by Structural Analysis

Curr Biol. 2000 May 4;10(9):517-25. doi: 10.1016/s0960-9822(00)00467-x.

Abstract

Background: Proteins such as HP1, found in fruit flies and mammals, and Swi6, its fission yeast homologue, carry a chromodomain (CD) and a chromo shadow domain (CSD). These proteins are required to form functional transcriptionally silent centromeric chromatin, and their mutation leads to chromosome segregation defects. CSDs have only been found in tandem in proteins containing the related CD. Most HP1-interacting proteins have been found to associate through the CSD and many of these ligands contain a conserved pentapeptide motif.

Results: The 1.9 A crystal structure of the Swi6 CSD is presented here. This reveals a novel dimeric structure that is distinct from the previously reported monomeric nuclear magnetic resonance (NMR) structure of the CD from the mouse modifier 1 protein (MoMOD1, also known as HP1beta or M31). A prominent pit with a non-polar base is generated at the dimer interface, and is commensurate with binding an extended pentapeptide motif. Sequence alignments based on this structure highlight differences between CDs and CSDs that are superimposed on a common structural core. The analyses also revealed a previously unrecognised circumferential hydrophobic sash around the surface of the CD structure.

Conclusions: Dimerisation through the CSD of HP1-like proteins results in the simultaneous formation of a putative protein-protein interaction pit, providing a potential means of targeting CSD-containing proteins to particular chromatin sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Dimerization
  • Fungal Proteins / chemistry*
  • Fungal Proteins / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Conformation*
  • Protein Folding
  • Saccharomyces cerevisiae Proteins*
  • Schizosaccharomyces / chemistry
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism

Substances

  • Fungal Proteins
  • SWI6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors