The relationship between relative solvent accessible surface area (rASA) and irregular structures in protean segments (ProSs)

Abstract

Intrinsically Disordered Proteins (IDPs) lack a stable, three-dimensional structure under physiological conditions, yet they exhibit numerous biological activities. Protean segments (ProSs) are the functional regions of intrinsically disordered proteins that undergo disorder-to-order transitions upon binding to their partners. Example ProSs collected from the intrinsically disordered proteins with extensive annotations and literature (IDEAL) database. The interface of protean segments (ProSs) is classified into core, rim, and support, and analyzed their secondary structure elements (SSEs) based on the relative accessible surface area (rASA). The amino acid compositions and the relative solvent accessible surface areas (rASAs) of ProS secondary structural elements (SSEs) at the interface, core and rim were compared to those of heterodimers. The average number of contacts of alpha helices and irregular residues was calculated for each ProS and heterodimer. Furthermore, the ProSs were classified into high and low efficient based on their average number of contacts at the interface. The results indicate that the irregular structures of ProSs and heterodimers are significantly different. The rASA of irregular structures in the monomeric state (rASAm) is large, leads to the formation of larger ΔrASA and many contacts in ProSs. Keywords: Intrinsically disordered proteins, secondary structure elements (SSEs), protein interface, relative solvent accessible surface area (rASA), protein-protein interactions, protean segments (ProSs). Background: An intrinsically disordered protein (IDP) is a protein that is disordered (as a whole or in part) in the unbound state and undergoes a disorder-to-order transition upon binding to their partners [1-3]. These IDPs have numerous biological activities such as signal transduction and transcriptional regulation and are highly abundant in nature [2, 4]. These proteins are associated with various human diseases, including cancer, cardiovascular disease, neurodegenerative diseases and amyloidoses [5-7]. Due to their role in various biological processes and their involvement in various diseases, IDPs are the focus of many biomedical-related areas and represent attractive novel drug targets [7, 8].