Transporter BetP - Oligomeric Structure, Transport Catalysis and Regulation

Abstract

The Na+ coupled betaine uptake system BetP of Corynebacterium glutamicum belongs to the BCCT family of transporters and comprises both a catalytic function (betaine/Na+ cotransport) and a sensory/regulatory function (responding to osmotic stress). Its 2D (electron crystallography) and 3D structure (X-ray crystallography) has been solved. Within a homooligomeric trimer, each BetP protomer harbours both an N- and a C-terminal domain involved in stimulus sensing and intramolecular signal transduction. Factors known so far contributing to the sensory and regulatory function of BetP are (i) the two terminal domains, (ii) K+ ions as an osmostress related stimulus, and (iii) interaction with the surrounding membrane. The primary stimulus of BetP, the rise in the cytoplasmic K+ concentration, has been elucidated using a proteoliposomal system, whereas the second stimulus, attributed to changes in the physical state of the surrounding membrane was investigated in intact cells.Intramolecular signal transduction of the two different stimuli involves contributions from individual domains of BetP protomers and is essentially based on its oligomeric (homotrimeric) structure. We have now analyzed interaction of the three individual protomers of BetP in mechanistic terms by using novel heterooligomeric constructs of BetP composed of three structurally different protomers. On the basis of these studies we suggest a functional model of intersubunit crosstalk between the three individual BetP monomers as well as the terminal domains of BetP during its catalytic and its sensory function.