The Distinct Properties of the Consecutive Disordered Regions Inside or Outside Protein Domains and Their Functional Significance.

Huqiang Wang,Chao Gao,Jiayin Zang,Haolin Zhong,Dong Yang

doi:10.3390/ijms221910677

Huqiang Wang, Chao Gao + Show 3 more

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https://doi.org/10.3390/ijms221910677

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Abstract

The consecutive disordered regions (CDRs) are the basis for the formation of intrinsically disordered proteins, which contribute to various biological functions and increasing organism complexity. Previous studies have revealed that CDRs may be present inside or outside protein domains, but a comprehensive analysis of the property differences between these two types of CDRs and the proteins containing them is lacking. In this study, we investigated this issue from three viewpoints. Firstly, we found that in-domain CDRs are more hydrophilic and stable but have less stickiness and fewer post-translational modification sites compared with out-domain CDRs. Secondly, at the protein level, we found that proteins with only in-domain CDRs originated late, evolved rapidly, and had weak functional constraints, compared with the other two types of CDR-containing proteins. Proteins with only in-domain CDRs tend to be expressed spatiotemporal specifically, but they tend to have higher abundance and are more stable. Thirdly, we screened the CDR-containing protein domains that have a strong correlation with organism complexity. The CDR-containing domains tend to be evolutionarily young, or they changed from a domain without CDR to a CDR-containing domain during evolution. These results provide valuable new insights about the evolution and function of CDRs and protein domains.

Highlights

Accepted: 29 September 2021Intrinsically disordered proteins (IDPs) often have variable structures and functions and play an important role in the regulation of complex biological processes [1,2]
Lower stickiness scores mean the DomCDRs avoid promiscuous interactions (Figure 2D, Table S1), while at the same time, DomCDRs showed fewer PTM sites compared with NonDomCDRs (Figure 2E, Table S1)
We focused on the differences between consecutive disordered regions (CDRs) inside and outside protein domains and their functional relevance to the proteins containing these two types of

Summary

Introduction

Disordered proteins (IDPs) often have variable structures and functions and play an important role in the regulation of complex biological processes [1,2]. The CDRs in IDPs play an important role in the transition of structure and function, contributing to the formation of functional diversity and system complexity [4]. Previous studies have found that CDRs may be located inside or outside the protein domains (referring to all Pfam-A domains in this study) [1,5,6,7]. According to the relative location, CDRs are divided into two types: CDRs inside protein domains (DomCDRs) and CDRs outside protein domains (NonDomCDRs) (Figure 1A). The difference between DomCDRs and NonDomCDRs is largely unknown

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