Dimerisation of a chrome shadow domain and distinctions from the chromodomain as revealed by structural analysis

Background: Proteins such as HPI, found in fruit flies and mammals, and Swi 6, its fission yeast homologue, carry a chromodomain (CD) and a chrome shad ow domain (CSD). These proteins are required to form functional transcripti onally silent centromeric chromatin, and their mutation leads to chromosome segregation defects. CSDs have only been found in tandem in proteins conta ining the related CD. Most HP1-interacting proteins have been found to asso ciate through the CSD and many of these ligands contain a conserved pentape ptide motif. Results: The 1.9 Angstrom crystal structure of the Swi6 CSD is presented he re. This reveals a novel dimeric structure that is distinct from the previo usly reported monomeric nuclear magnetic resonance (NMR) structure of the C D from the mouse modifier 1: protein (MoMOD1, also known as HP1 beta or M31 ). A prominent pit with a non-polar base is generated at the dimer interfac e, and is commensurate with binding an extended pentapeptide motif. Sequenc e alignments based on this structure highlight differences between CDs and CSDs that are superimposed on a common structural core. The analyses also r evealed a previously unrecognised circumferential hydrophobic sash around t he surface of the CD structure. Conclusions: Dimerisation through the CSD of HP1-like proteins results in t he simultaneous formation of a putative protein-protein interaction pit, pr oviding a potential means of targeting CSD-containing proteins to particula r chromatin sites.