Exploring the Functional Landscape of the P53 Regulatory Domain: The Stabilizing Role of Post-Translational Modifications

Overview

Journal J Chem Theory Comput

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2024 Jul 8

PMID 38973087

Authors

Michael J Bakker

Oskar Svensson

Henrik V So Rensen

Marie Skepo

Affiliations

Soon will be listed here.

Abstract

This study focuses on the intrinsically disordered regulatory domain of p53 and the impact of post-translational modifications. Through fully atomistic explicit water molecular dynamics simulations, we show the wealth of information and detailed understanding that can be obtained by varying the number of phosphorylated amino acids and implementing a restriction in the conformational entropy of the N-termini of that intrinsically disordered region. The take-home message for the reader is to achieve a detailed understanding of the impact of phosphorylation with respect to (1) the conformational dynamics and flexibility, (2) structural effects, (3) protein interactivity, and (4) energy landscapes and conformational ensembles. Although our model system is the regulatory domain p53 of the tumor suppressor protein p53, this study contributes to understanding the general effects of intrinsically disordered phosphorylated proteins and the impact of phosphorylated groups, more specifically, how minor changes in the primary sequence can affect the properties mentioned above.

Citing Articles

Deeper Insight of the Conformational Ensemble of Intrinsically Disordered Proteins.

Svensson O, Bakker M, Skepo M J Chem Inf Model. 2024; 64(15):6105-6114.

PMID: 39056166 PMC: 11323008. DOI: 10.1021/acs.jcim.4c00941.

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