Evolutionary Study of Disorder in Protein Sequences

Abstract

Intrinsically disordered proteins (IDPs) contain regions lacking intrinsic globular structure (intrinsically disordered regions, IDRs). IDPs are present across the tree of life, with great variability of IDR type and frequency even between closely related taxa. To investigate the function of IDRs, we evaluated and compared the distribution of disorder content in 10,695 reference proteomes, confirming its high variability and finding certain correlation along the Euteleostomi (bony vertebrates) lineage to number of cell types. We used the comparison of orthologs to study the function of disorder related to increase in cell types, observing that multiple interacting subunits of protein complexes might gain IDRs in evolution, thus stressing the function of IDRs in modulating protein-protein interactions, particularly in the cell nucleus. Interestingly, the conservation of local compositional biases of IDPs follows residue-type specific patterns, with E- and K-rich regions being evolutionarily stable and Q- and A-rich regions being more dynamic. We provide a framework for targeted evolutionary studies of the emergence of IDRs. We believe that, given the large variability of IDR distributions in different species, studies using this evolutionary perspective are required.

The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin

“…Other frequent CBRs are G-, A-, K-, Q-, and P-rich, with full conservation not being so separated from the rest of the patterns. These results agree with the general stability previously observed for E-rich regions and the more dynamic behavior observed for Q-rich regions [ 7 ]. Most of the CBR conservation patterns indicate conservation in one or very few species, indicating fast selection.…”

“…It is known that there are differences in the conservation patterns of CBRs [ 7 ] and polyX [ 34 ] depending on the type of amino acid. We show the main conservation patterns by amino acid type in HTT interactors in Supplementary Figure S2 .…”

“…We previously applied this hypothesis to study the correlation between orthologs conserved across five metazoan species [ 7 ]. Here we apply this approach in a more focused way to find IDR correlations between HTT and the eleven WW-domain containing HTT interactors, to try to get information on the mode of interaction of these proteins with HTT.…”

“…The study of the function of LCRs is therefore necessary to understand protein functions, particularly protein interactions, but this is both experimentally and computationally complex due to their structural properties and low conservation [ 6 ]. Evolutionary approaches to compare LCR usage across selected sets of species have been used to categorize LCRs and learn about their significance and function in different contexts [ 7 ]. Here, we will illustrate how to examine LCRs in HTT and interactors, using a similar evolutionary approach to examine possible functions of LCRs in the interaction of HTT with partner proteins.…”

A new type of disordered CP12 protein in the marine diatom Thalassiosira pseudonana

“…The CP12 proteins from C. reinhardtii, A. thaliana and S. elongatus have been extensively studied and shown to belong to the IDP family. IDPs, or in other words ductile, dancing, malleable or exible proteins [49], are common in various proteomes [50][51][52][53][54][55] and occupy a unique structural and functional niche in which function is directly linked to structural disorder [47,[56][57][58]. The expression of CP12 from the diatom T. pseudonana is constitutively expressed under dark and light conditions, as well as during the growth, unlike CP12 from A. thaliana that is co-expressed with PRK and GAPDH in the light [59].…”