Trimethylamine N-oxide alters structure-function integrity of β-casein: Structural disorder co-regulates the aggregation propensity and chaperone activity.

Intrinsically disordered proteins (IDPs), involved in the regulation and function of various cellular processes like transcription, translation, cell cycle etc., exist as ensembles of rapidly interconverting structures with functional plasticity. Among numerous cellular regulatory mechanisms involved in structural and functional regulation of IDPs, osmolytes are emerging as promising regulatory agents due to their ability to affect the structure-function integrity of IDPs. The present study investigated the effect of methylamine osmolytes on β-casein, an IDP essential for maintaining the overall stability of casein complex in milk. It was observed that trimethylamine N-oxide induces a compact structural state in β-casein with slightly decreased chaperone activity and insignificant aggregation propensity. However, the other two osmolytes from this group, i.e., sarcosine and betaine, had no significant effect on the overall structure and chaperone activity of the IDP. The present study hints towards the possible evolutionary selection of higher structural disorder in β-casein, compared to α-casein, for stability of the casein complex and prevention of amyloidosis in the mammary gland. [ABSTRACT FROM AUTHOR]