2.A.1.6.4
(Proline/glycine-betaine):(H⁺/Na⁺) symporter, ProP (also transports taurine, ectoine, pipecolate, proline-betaine, N,N-dimethylglycine, carnitine, and 1-carboxymethyl-pyridinium) (subject to osmotic activation). Transmembrane helix I and periplasmic loop 1 are involved in osmosensing and osmoprotectant transport (Keates et al., 2010). ProP detects the increase in cytoplasmic cation concentration associated with osmotically induced cell dehydration and mediates osmolyte uptake into bacteria (Ozturk et al. 2020). ProP is a 12-TMS protein with an α-helical, cytoplasmic C-terminal domain (CTD) linked to TMS XII. The CTD helix associates with the anionic membrane surface to lock ProP in an inactive conformation. The release of the CTD may activate ProP. Molecular dynamics simulations showed specific intrapeptide salt bridges forming when the CTD associated with the membrane. The salt bridge Lys447-Asp455 weakened CTD-lipid interactions at 0.25 M KCl, and gradual stiffening of the membrane with increasing salinity was obseerved. Thus, salt cations may affect CTD release and activate ProP by increasing the order of membrane phospholipids (Ozturk et al. 2020). ProP forestalls cellular dehydration by detecting environments with high osmotic pressure and mediating the accumulation of organic osmolytes by bacterial cells. Structural determinants and functional significance of dimerization have been described (Ozturk et al. 2023).