Influence of sequence length and charged residues on Swc5 binding with histone H2A-H2B.

Abstract

SWR is a member of chromatin remodeler family and participates the replacement of histone H2A with H2A.Z. One of the SWR subunits, Swc5, has an intrinsically disordered region and binds to H2A-H2B dimer. Though the binding structure of Swc5 and H2A-H2B has been resolved recently, it is still challenging to investigate the binding mechanism as well as the role of the charge interactions between Swc5 and H2A-H2B. Here we developed a coarse-grained structure-based model and performed molecular dynamics simulations to investigate the binding processes of two Swc5 regions with different lengths (swc5-a and swc5-b) to H2A-H2B. The simulation results suggest a different role of electrostatic interactions between swc5-a/swc5-b and H2A-H2B on binding. The electrostatic interactions between swc5-a/swc5-b and H2A-H2B can not only accelerate the initial capture step of binding, but can also trap the swc5-a/swc5-b at the wrong binding site on H2A. Besides, the conserved DEF/Y-2 motif of Swc5 is important for the binding affinity and the recognition with H2A-H2B at the initial step. Both swc5-a and swc5-b undergo a structural shift before reaching the final bound state. This theoretical study provides important details and the underlying physical mechanisms of the binding processes of swc5-a/swc5-b and H2A-H2B.