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Analysis of the relationships between evolvability, thermodynamics, and the functions of intrinsically disordered proteins/regions

Paper ID Volume ID Publish Year Pages File Format Full-Text
15161 1383 2012 7 PDF Available
Title
Analysis of the relationships between evolvability, thermodynamics, and the functions of intrinsically disordered proteins/regions
Abstract

The evolvability of proteins is not only restricted by functional and structural importance, but also by other factors such as gene duplication, protein stability, and an organism's robustness. Recently, intrinsically disordered proteins (IDPs)/regions (IDRs) have been suggested to play a role in facilitating protein evolution. However, the mechanisms by which this occurs remain largely unknown. To address this, we have systematically analyzed the relationship between the evolvability, stability, and function of IDPs/IDRs. Evolutionary analysis shows that more recently emerged IDRs have higher evolutionary rates with more functional constraints relaxed (or experiencing more positive selection), and that this may have caused accelerated evolution in the flanking regions and in the whole protein. A systematic analysis of observed stability changes due to single amino acid mutations in IDRs and ordered regions shows that while most mutations induce a destabilizing effect in proteins, mutations in IDRs cause smaller stability changes than in ordered regions. The weaker impact of mutations in IDRs on protein stability may have advantages for protein evolvability in the gain of new functions. Interestingly, however, an analysis of functional motifs in the PROSITE and ELM databases showed that motifs in IDRs are more conserved, characterized by smaller entropy and lower evolutionary rate, than in ordered regions. This apparently opposing evolutionary effect may be partly due to the flexible nature of motifs in IDRs, which require some key amino acid residues to engage in tighter interactions with other molecules. Our study suggests that the unique conformational and thermodynamic characteristics of IDPs/IDRs play an important role in the evolvability of proteins to gain new functions.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Intrinsically disordered regions have higher evolutionary rates than ordered regions. ► Mutations in disordered regions cause less stability changes than in ordered regions. ► Functional motifs in disordered regions are more conserved than in ordered regions. ► Evolvability, thermodynamics and function of disordered regions are inter-related.

Keywords
Disordered proteins; Protein evolvability; Protein stability; Function
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Analysis of the relationships between evolvability, thermodynamics, and the functions of intrinsically disordered proteins/regions
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 41, December 2012, Pages 51–57
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us