How to evict HP1 from H3: Using a complex salt bridge

Biophys Chem. 2023 Sep:300:107062. doi: 10.1016/j.bpc.2023.107062. Epub 2023 Jun 7.

Abstract

In an effort to unravel the unknown "binary switch" mechanisms underlying the "histone code" hypothesis of gene silencing and activation, we study the dynamics of Heterochromatin Protein 1 (HP1). We find in the literature that when HP1 is bound to tri-methylated Lysine9 (K9me3) of histone-H3 through an aromatic cage consisting of two tyrosines and one tryptophan, it is evicted upon phosphorylation of Serine10 (S10phos) during mitosis. In this work, the kick-off intermolecular interaction of the eviction process is proposed and described in detail on the basis of quantum mechanical calculations: specifically, an electrostatic interaction competes with the cation-π interaction and draws away K9me3 from the aromatic cage. An arginine, abundant in the histonic environment, can form an intermolecular "complex salt bridge" with S10phos and dislodge HP1. The study attempts to reveal the role of phosphorylation of Ser10 on the H3 tail in atomic detail.

Keywords: Complex salt bridge; Heterochromatin Protein 1 HP1; Histone H3; Post translational modifications; Protein-protein interaction; S10 phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromobox Protein Homolog 5*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Histones*
  • Humans
  • Phosphorylation
  • Protein Binding

Substances

  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone
  • Histones
  • CBX1 protein, human