期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 79, 期 1, 页码 -出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-021-04087-z
关键词
TMAO; Protein misfolding; Proline; Cis-trans isomerization
资金
- DST PURSE
- CSIR [09/045(1619)/2019-EMR-I, 09/045(1359)/2015-EMR-I]
- MG Grant
TMAO is a significant metabolite derived from various organic compounds, with diverse biological functions in humans. Studies have shown its crucial impact on protein folding and cell cycle, potentially leading to protein misfolding and the development of related diseases.
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.
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