乙酰化
磷酸化
化学
分子动力学
内在无序蛋白质
生物物理学
组蛋白
生物化学
细胞生物学
生物
计算化学
基因
作者
Anamika Ghosh,Debabani Ganguly
标识
DOI:10.1080/07391102.2023.2279270
摘要
The C-terminal of tumor suppressor protein p53 is intrinsically disordered while unbound. This particular segment often shows structural plasticity when bound to other binding partners. The disordered component undergoes a disordered to ordered transition upon recognition. Post-translational modifications (PTMs), namely phosphorylation and acetylation, significantly alter the structural motifs of the segment. Among the various types of PTMs, phosphorylation, and acetylation of p53 at both N- and C- terminals lead to stabilization and activation. It has been noted experimentally that phosphorylation often regulates (enhances or reduces) the acetylation at specific sites. The phosphorylation of Thr377 and Ser378 reduces the acetylation of Lys373 and Lys382. Mutations of Thr377 and Ser378 to neutral Ala enhance and phospho mimic Asp reduce the acetylation of Lys373 and Lys382. Simulations of several single-point and pair-wise mutated systems have been generated to compare how the presence or absence of phosphorylation favors or disfavors the acetylation by thermodynamic and conformational analysis. We are using implicit solvent replica exchange molecular dynamics simulations to get 200 ns well-converged conformational ensembles of each system. Different sets of systems having both single and double PTMs are simulated. The results admit the appreciable change in the secondary structural level upon specific PTM. Also, the residual structure of the unbound p53 with single-point PTM varies significantly with pair-wise modifications. These observations further shed light on the relationship between the interdependencies of the specific PTM sites and the secondary structural levels.Communicated by Ramaswamy H. Sarma.
科研通智能强力驱动
Strongly Powered by AbleSci AI