Taurine Induces an Ordered but Functionally Inactive Conformation in Intrinsically Disordered Casein Proteins

Mohd Younus Bhat,Laishram Rajendrakumar Singh,Tanveer Ali Dar

doi:10.1038/s41598-020-60430-7

Mohd Younus Bhat, Laishram Rajendrakumar Singh + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-60430-7

Copy DOI

Abstract

Intrinsically disordered proteins (IDPs) are involved in various important biological processes, such as cell signalling, transcription, translation, cell division regulation etc. Many IDPs need to maintain their disordered conformation for proper function. Osmolytes, natural organic compounds responsible for maintaining osmoregulation, have been believed to regulate the functional activity of macromolecules including globular proteins and IDPs due to their ability of modulating the macromolecular structure, conformational stability, and functional integrity. In the present study, we have investigated the effect of all classes of osmolytes on two model IDPs, α- and β-casein. It was observed that osmolytes can serve either as folding inducers or folding evaders. Folding evaders, in general, do not induce IDP folding and therefore had no significant effect on structural and functional integrity of IDPs. On the other hand, osmolytes taurine and TMAO serve as folding inducers by promoting structural collapse of IDPs that eventually leads to altered structural and functional integrity of IDPs. This study sheds light on the osmolyte-induced regulation of IDPs and their possible role in various disease pathologies.

Highlights

A well-defined, stable three dimensional structure was once thought to be an essential pre-requisite for proper function of a protein[1,2,3]
These osmolytes have been grouped into three main classes: polyols and sugars; amino acids and their derivatives (β-alanine and taurine), and methylamines (trimethylamine N-oxide (TMAO), sarcosine and betaine
At least two osmolytes were chosen from each class, with the exception for methylamines as their effect on the same protein system has been already published from our laboratory29

Summary

Introduction

A well-defined, stable three dimensional structure was once thought to be an essential pre-requisite for proper function of a protein[1,2,3]. The absence of stable structure allows these proteins to exist as highly dynamic conformational ensembles containing a wide variety of rapidly interconverting structures, thereby providing means for interaction with multiple often unrelated partners and for performing various important physiological functions[12,15,16,17,18,19] These proteins once known as a small group of rare exceptions are being presently explored for their central roles in the regulation of various key cellular processes including signal transduction and molecular recognition, mRNA metabolism, translation, transcription, and cell cycle[8,10,15,18,20,21]. The study hints that unwanted production and/or accumulation of certain osmolytes at high levels may alter structure and function of certain IDPs and underlie pathophysiology of various diseases

Methods

Results

Conclusion