Journal of Bioremediation & Biodegradation
Open Access

Abstract

Protein post translational modifications, such as glycosylation, acetylation, or phosphorylation, are widespread phenomena in cellular physiology. In our study, we focus on post translational modification (PTM) of a cold, pain, and newly recognized testosterone receptor, TRPM8 by a polyester comprised of repeated units of R-3-hydroxybutyrate, which forms a polymeric chain, poly-(R)-3-hydroxybutyrate (PHB). We term this modification PHBylation by analogy with the known protein modifications. However, PHBylation stands out of other PTMs that it is a covalent and permanent attachment of a large hydrophobic polymer that introduces significant conformational changes on the channel protein and therefore impacts its function. Along with PHB, we discovered that TRPM8 is modified with inorganic polyphosphate (polyP), where both polymers essentially contribute to the channel structure/function relationship. We found that PHB was critical for the temperature and ligand-induced TRPM8 channel activity. Furthermore, PHB mediated ligand binding to the channel, while polyP contributed to its voltage-sensitivity. These results indicate that TRPM8 functions in a form of supramolecular complexes with PHB and polyP. The formation of such complexes offers a new concept for model of a mammalian ion channel. It proposes indispensable roles of these PTMs, reflecting (a) temperature- or ligand-induced conformational changes that translate to channel gating; (b) proper protein folding and localization to the plasma membrane; and (c) PHB-poly P-rendered structure of anion-conducting core within the protein, which ensures ion selection and conduction along the uniform energy profile lining the internal cavity between both polymers.

Biography

Email: zakharel@uic.edu