3gv6 Citations

Recognition and specificity determinants of the human cbx chromodomains.

J Biol Chem 286 521-9 (2011)
Related entries: 2l11, 2l12, 2l1b, 3fdt, 3h91, 3i90, 3i91

Cited: 163 times
EuropePMC logo PMID: 21047797

Abstract

The eight mammalian Cbx proteins are chromodomain-containing proteins involved in regulation of heterochromatin, gene expression, and developmental programs. They are evolutionarily related to the Drosophila HP1 (dHP1) and Pc (dPc) proteins that are key components of chromatin-associated complexes capable of recognizing repressive marks such as trimethylated Lys-9 and Lys-27, respectively, on histone H3. However, the binding specificity and function of the human homologs, Cbx1-8, remain unclear. To this end we employed structural, biophysical, and mutagenic approaches to characterize the molecular determinants of sequence contextual methyllysine binding to human Cbx1-8 proteins. Although all three human HP1 homologs (Cbx1, -3, -5) replicate the structural and binding features of their dHP counterparts, the five Pc homologs (Cbx2, -4, -6, -7, -8) bind with lower affinity to H3K9me3 or H3K27me3 peptides and are unable to distinguish between these two marks. Additionally, peptide permutation arrays revealed a greater sequence tolerance within the Pc family and suggest alternative nonhistone sequences as potential binding targets for this class of chromodomains. Our structures explain the divergence of peptide binding selectivity in the Pc subfamily and highlight previously unrecognized features of the chromodomain that influence binding and specificity.

Articles - 3gv6 mentioned but not cited (3)

  1. Recognition and specificity determinants of the human cbx chromodomains. Kaustov L, Ouyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney GA, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH. J Biol Chem 286 521-529 (2011)
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  3. Protein folding, misfolding and aggregation: The importance of two-electron stabilizing interactions. Cieplak AS. PLoS One 12 e0180905 (2017)


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