Peptide recognition by heterochromatin protein 1 (HP1) chromoshadow domains revisited: Plasticity in the pseudosymmetric histone binding site of human HP1.

Heterochromatin protein 1 (HP1), a highly conserved non-histone chromosomal protein in eukaryotes, plays important roles in the regulation of gene transcription. Each of the three human homologs of HP1 includes a chromoshadow domain (CSD). The CSD interacts with various proteins bearing the P X V X L motif but also with a region of histone H3 that bears the similar P XX V X L motif. The latter interaction has not yet been resolved in atomic detail. Here we demonstrate that the CSDs of all three human HP1 homologs have comparable affinities to the P XX V X L motif of histone H3. The HP1 C-terminal extension enhances the affinity, as does the increasing length of the H3 peptide. The crystal structure of the human HP1γ CSD (CSDγ ) in complex with an H3 peptide suggests that recognition of H3 by CSDγ to some extent resembles CSD-P X V X L interaction. Nevertheless, the prolyl residue of the P XX V X L motif appears to play a role distinct from that of Pro in the known HP1β CSD-P X V X L complexes. We consequently generalize the historical CSD-P X V X L interaction model and expand the search scope for additional CSD binding partners.