Analysis of Structural Changes in the Protein near the Phosphorylation Site

Abstract

Modification of the protein after synthesis (PTM) often affects protein function as supported by numerous studies. However, there is no consensus about the degree of structural protein changes after modification. For phosphorylation of serine, threonine, and tyrosine, which is a common PTM in the biology of living organisms, we consider topical issues related to changes in the geometric parameters of a protein (Rg, RMSD, Cα displacement, SASA). The effect of phosphorylation on protein geometry was studied both for the whole protein and at the local level (i.e., in different neighborhoods of the modification site). Heterogeneity in the degree of protein structural changes after phosphorylation was revealed, which allowed for us to isolate a group of proteins having pronounced local structural changes in the neighborhoods of up to 15 amino acid residues from the modification site. This is a comparative study of protein structural changes in neighborhoods of 3–15 amino acid residues from the modified site. Amino acid phosphorylation in proteins with pronounced local changes caused switching from the inactive functional state to the active one.

Normal Mode Analysis Elicits Conformational Shifts in Proteins at Both Proximal and Distal Regions to the Phosphosite Stemming from Single-Site Phosphorylation

“…Therefore, despite the differences in resolution and computational methodologies between ANM-NMA and all-atom NMA, their agreement reinforces the validity and reliability of our conclusions. A recent study analyzed protein structural changes within neighborhoods of 3–15 amino acid residues from phosphorylation sites, focusing on alterations in geometric parameters such as the radius of gyration ( R g ), RMSD, Cα displacement, and SASA . What sets our study apart is its systematic approach to comprehensively exploring the impact of single-site phosphorylation on protein structure and dynamics.…”

“…A recent study analyzed protein structural changes within neighborhoods of 3–15 amino acid residues from phosphorylation sites, focusing on alterations in geometric parameters such as the radius of gyration ( R g ), RMSD, Cα displacement, and SASA. 31 What sets our study apart is its systematic approach to comprehensively exploring the impact of single-site phosphorylation on protein structure and dynamics. We employ stringent filtration criteria applied to the data set to ensure robustness and reliability in the observations.…”