Please contact:

Dr. Inga Hänelt
Junior Professor
Biocenter N220/1.03
phone +49-69-798 29 261

Structure and function of different members of the superfamily of K(+) transporters

The Ktr/Trk/HKT family unites proteins from all kingdoms of life but animals that translocate K(+) and/or Na(+) over the plasma membrane. These proteins are key components of osmotic regulation, pH homeostasis and resistance to high salinity and dryness. Ktr/Trk/HKT proteins are closely related to K(+) channels like KcsA but also show several striking differences which are assigned to an altered function.

Although crystal structures of the bacterial K(+) uptake system KtrAB are available, its physiology is not understood. Does KtrAB function as channel or as Na(+)/K(+) symporter? Which regulatory role plays ATP bound to KtrA and furthermore how does KtrA affect the structure and function of KtrB? Which mechanisms enable the controlled ion translocation?

Figure 1. Structure of KtrAB  viewed from within the plane of the membrane (center) and from the peri-plasmic side (right). The translocation pathway within KtrB is highlighted (left). Translocating subunits KtrB shown in blue, bound potassium ions in yellow, the regulatory gating rings formed by 8 KtrAs in red, bound ATP in turquois, transmembrane loop in green and selectivity filter-forming glycinyl residues in orange.

Other than for KtrAB the function of the KdpFABC system is well studied: It acts as an unusual P-type ATPase, in which ATP hydrolysis and substrate transport are spatially separated on two different subunits which, in turn, leads to a unique coupling mechanism. However, neither the coupling between ATP hydrolysis and K(+) translocation nor the general arrangements allowing active transport are understood.

Figure 2. Schematic overview of subunit organization within the KdpFABC complex of Escherichia coli. Although potassium translocation is mediated by the channel-like KdpA subunit, KdpB comprises all signature motifs of P-type ATPases with corresponding N-, A- and P-domains. The N-domain carries the ATP binding pocket. KdpF consists of just one transmembrane a-helix. The KdpC subunit is also anchored in the membrane by one helix; the remainder of the polypeptide protrudes into the cytoplasm.

Beyond studying a single family of proteins, whose members were shown to be essential for the survival of (pathogenic) organisms, the opportunity arises to study general features, commonalities and differences, of transporters and channels. Today’s data suggest that KtrAB and KdpFABC represent evolutionary intermediates between channels and transporters in which a former channel is converted into a transporter by additional, non-covalently linked regulatory subunits. By our multidisciplinary approaches we will add a deeper understanding on the structural basis for ion transporters and channels in general.