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

Journal Article · · Journal of Biological Chemistry

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 PXVXL motif but also with a region of histone H3 that bears the similar PXXVXL 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 PXXVXL 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-PXVXL interaction. Nevertheless, the prolyl residue of the PXXVXL motif appears to play a role distinct from that of Pro in the known HP1β CSD-PXVXL complexes. Lastly, we consequently generalize the historical CSD-PXVXL interaction model and expand the search scope for additional CSD binding partners.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Natural Science Foundation of China (NSFC); AbbVie, Boehringer Ingelheim; Canadian Inst. of Health Research (CIHR); Ontario Genomics Inst.; Ontario Ministry of Economic Development and Innovation; Wellcome Trust
Grant/Contract Number:
AC02-06CH11357; 31500613; OGI-055; 092809/Z/10/Z
OSTI ID:
1368285
Journal Information:
Journal of Biological Chemistry, Vol. 292, Issue 14; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

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Cited By (2)

HP1 reshapes nucleosome core to promote phase separation of heterochromatin journal October 2019
NBS1 interacts with HP1 to ensure genome integrity journal December 2019