The Gut Metabolite, Trimethylamine N-oxide Inhibits Protein Folding by Affecting Cis–trans Isomerization and Induces Cell Cycle Arrest
TMAO, Protein Misfolding, Proline, Cis–trans Isomerization
Digital Object Identifier (DOI)
Trimethylamine N-Oxide (TMAO) is an important metabolite, which is derived from choline, betaine, and carnitine in various organisms. In humans, it is synthesized through gut microbiota and is abundantly found in serum and cerebrospinal fluid (CSF). Although TMAO is a stress protectant especially in urea-rich organisms, it is an atherogenic agent in humans and is associated with various diseases. Studies have also unveiled its exceptional role in protein folding and restoration of mutant protein functions. However, most of these data were obtained from studies carried on fast-folding proteins. In the present study, we have investigated the effect of TMAO on the folding behavior of a well-characterized protein with slow folding kinetics, carbonic anhydrase (CA). We discovered that TMAO inhibits the folding of this protein via its effect on proline cis–trans isomerization. Furthermore, TMAO is capable of inducing cell cycle arrest. This study highlights the potential role of TMAO in developing proteopathies and associated diseases.
Was this content written or created while at USF?
Citation / Publisher Attribution
Cellular and Molecular Life Sciences, v. 79, art. 12
Scholar Commons Citation
Kumari, Kritika; Warepam, Marina; Bansal, Aniket Kumar; Dar, Tanveer Ali; and Uversky, Vladimir N., "The Gut Metabolite, Trimethylamine N-oxide Inhibits Protein Folding by Affecting Cis–trans Isomerization and Induces Cell Cycle Arrest" (2021). Molecular Medicine Faculty Publications. 1011.