Molecular mechanism of betaine transport and stress regulation by the Na+-coupled symporter BetP

The Na⁺-coupled symporter BetP, a member of the Betaine-Choline-Carnitine-Transporter (BCCT) family catalyzes uptake of the osmolyte betaine in Corynebacterium glutamicum. BetP also senses hyperosmotic stress and regulates its own activity according to the stress level. X-ray structures of BetP in different conformations reveal the translocation pathway of sodium and betaine towards the cytoplasm. Furthermore structural and functional data on single point mutants of BetP that exhibit changed substrate and co-substrate specificity elucidate the coupling mechanism in BetP.

BetP adjusts its transport rate according to the external osmotic conditions. The stress stimulus sensed by BetP is the cytoplasmic K⁺ concentration, which increases immediately with increasing external osmolality. BetP regulates activity only when it is trimeric as shown by mutagenesis and functional analysis. Intra-trimeric interactions lock individual protomers in distinct conformations of the catalytic and regulatory cycle and specific lipid-protein interactions play an additional role in transport activation and regulation. K⁺-activation of BetP is facilitated by a sophisticated interaction network between individual protomers in which lipids participate in the formation of K⁺ binding sites.