Importance of Electrostatic Interactions in the Association of Intrinsically Disordered Histone Chaperone Chz1 and Histone H2A.Z-H2B

• DOI: 10.1371/journal.pcbi.1002608
• Publication Date: 2012-07-13T20:37:09Z
• Authors: Xiakun Chu; Yong Wang; Linfeng Gan; Yawen Bai; Wei Han; Erkang Wang; Jin Wang
• Keywords: Folding (DSP implementation); Chaperone (clinical); Electrostatics; Static electricity; Intrinsically Disordered Proteins

Histone chaperones facilitate assembly and disassembly of nucleosomes. Understanding the process how histone associate dissociate from histones can help clarify their roles in chromosome metabolism. Some are intrinsically disordered proteins (IDPs). Recent studies IDPs revealed that recognition biomolecules is realized by flexibility dynamics, challenging century-old structure-function paradigm. Here we investigate binding between chaperone Chz1 variant H2A.Z-H2B developing a structure-based coarse-grained model, which Debye-Hückel model implemented for describing electrostatic interactions due to highly charged characteristic H2A.Z-H2B. We find major structural changes only occur after rate-limiting dominant transition state undergoes folding coupled through two parallel pathways. Interestingly, although stabilize bound complex at first stage, rate formation not always accelerated slow escape conformations with non-native low salt concentrations. Our provide an ionic-strength-controlled binding/folding mechanism, leading cooperative mechanism "local collapse or trapping" "fly-casting" together new understanding IDPs' binding.