Specific Recognition Of Cbx Protein And Methylated Histone H3

In eukaryotic organisms,nucleosomes are the basic building blocks of chromatin.The nucleosome consists of an octamer formed by histones H2 A,H2B,H3 and H4 and DNA surrounding the octamer.Modification of histones(such as methylation,acetylation,etc.)alters the interaction of nucleosomes with DNA and downstream effector proteins,resulting in activation or inhibition of gene transcription.For methylation modification,further subdivision can be made according to the modification site and number: lysine mono,di,trimethylation,arginine mono,symmetrical di and asymmetric demethylation.These methylation modifications are regulated by a range of proteins,including methylases,demethylases,and methylation recognition proteins.In this paper,Cbx family proteins(including Cbx2,Cbx3,Cbx5,Cbx6 and Cbx7,etc.)were used as research objects,and the recognition mechanism of Lys-9 and Lys-27 methylation on H3 histones was studied by theoretical calculation.In the calculation section,we first predict the binding free energy using a combination of alanine scanning and interaction entropy(AS-IE).Using a histone peptide fragment containing trimethyl-Lys 9 / 27 as a model for 7 complex systems(Cbx3 / H3K9me3,Cbx5 / H3K9me3,Cbx6 / H3K9me3,Cbx7 / H3K9me3,Cbx2 / H3K27me3,Cbx6 / H3K27me3 and Cbx7 / H3K27me3)The free energy decomposition of a single residue was performed.The calculated results show that the calculated order of the strength of the Cbx family histone recognition methylation peptide is consistent with the reported experimental binding ability.Although the Cbx protein family is highly conserved,different Cbx proteins show significant differences in binding preferences.For example,Cbx6 and Cbx7 also show affinity for H3K9me3 and H3K27me3,and Cbx3 and Cbx5 have stronger binding to H3K9me3.Cbx2 tends to recognize H3K27me3.Based on the calculated results,we analyzed the specific source of recognition of the Cbx protein family from a quantitative perspective,and deepened our understanding of the interaction of the trimethylated histone-chromatin domain(Cbx protein).