Histone proteins play a significant role in gene regulation processes. Understanding the structure and interactions of the histone protein is very important to illustrate its bio-functionalities in the cellular processes of transcriptional activation, repression, chromatin assembly, and response to DNA damages. Recent studies found that mutations occurred at the H4 and H2B unit in the histone protein, such as H2B-E77K, H4-R93L, and H4-R97Q can cause various types of human tumors. To understand the mechanism of those mutations inducing the tumors at the atomistic level, we employed molecular dynamics (MD) simulations to investigate the structure and dynamics profiles of the histone protein with different mutations. In particular, it was found that the H2B-E77K mutation can make a semi-global conformational change and tend to separate the whole binding units-H4 and H2B. On the other hand, the other mutations, H4-R93L and H4-R97Q, resulted in a local and small conformational change by perturbing the residues near the binding interface. These results demonstrate that the electrostatic interactions between E77 in H2B and R93 in H4 are the dominating forces stabilizing the H4-H2B pair in the histone protein.

Mutation induced structure changes in histone proteins

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.