3q6s | pdb_00003q6s
The crystal structure of the heterochromatin protein 1 beta chromoshadow domain complexed with a peptide from Shugoshin 1
Structural highlights
Function[CBX1_HUMAN] Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane. [SGOL1_HUMAN] Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Isoform 3 plays a role in maintaining centriole cohesion involved in controlling spindle pole integrity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedHuman Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion during prophase and prevents premature sister-chromatid separation. Heterochromatin protein 1 (HP1) has been proposed to protect centromeric sister-chromatid cohesion by directly targeting Sgo1 to centromeres in mitosis. Here we show that HP1alpha is targeted to mitotic centromeres by INCENP, a subunit of the chromosome passenger complex (CPC). Biochemical and structural studies show that both HP1-INCENP and HP1-Sgo1 interactions require the binding of the HP1 chromo shadow domain to PXVXL/I motifs in INCENP or Sgo1, suggesting that the INCENP-bound, centromeric HP1alpha is incapable of recruiting Sgo1. Consistently, a Sgo1 mutant deficient in HP1 binding is functional in centromeric cohesion protection and localizes normally to centromeres in mitosis. By contrast, INCENP or Sgo1 mutants deficient in HP1 binding fail to localize to centromeres in interphase. Therefore, our results suggest that HP1 binding by INCENP or Sgo1 is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet uncharacterized interphase functions of CPC or Sgo1 at the centromeres. Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells.,Kang J, Chaudhary J, Dong H, Kim S, Brautigam CA, Yu H Mol Biol Cell. 2011 Apr 15;22(8):1181-90. doi: 10.1091/mbc.E11-01-0009. Epub 2011, Feb 23. PMID:21346195[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
