Pathways & interactions
Regulator of K+ conductance, C-terminal (IPR006037)
Short name: RCK_C
The regulator of K+ conductance (RCK) domain is found in many ligand-gated K+ channels, most often attached to the intracellular carboxy terminus. The domain is prevalent among prokaryotic K+ channels, and also found in eukaryotic, high-conductance Ca2+-activated K+ channels (BK channels) [PMID: 11292341, PMID: 11301020, PMID: 12037559]. Largely involved in redox-linked regulation of potassium channels, the N-terminal part of the RCK domain is predicted to be an active dehydrogenase at least in some cases [PMID: 11292341]. Some have a conserved sequence motif (G-x-G-x-x-G-x(n)-[DE]) for NAD+ binding [PMID: 8412700], but others do not, reflecting the diversity of ligands for RCK domains. The C-terminal part is less conserved, being absent in some channels, such as the kefC antiporter from Escherichia coli. It is predicted to bind unidentified ligands and to regulate sulphate, sodium and other transporters.
The X-ray structure of several RCK domains has been solved [PMID: 16227203, PMID: 11301020, PMID: 12037559]. It reveals an alpha-beta fold similar to dehydrogenase enzymes. The domain forms a homodimer, producing a cleft between two lobes. It has a composite structure, with an N-terminal (RCK-N), and a C-terminal (RCK-C) subdomain. The RCK-N subdomain forms a Rossmann fold with two alpha helices on one side of a six stranded parallel beta sheet and three alpha helices on the other side. The RCK-C subdomain is an all-beta-strand fold. It forms an extention of the dimer interface and further stabilises the RCK homodimer [PMID: 16227203, PMID: 11301020, PMID: 12037559]. Ca2+ is a ligand that opens the channel in a concentration-dependent manner. Two Ca2+ ions are located at the base of a cleft between two RCK domains, coordinated by the carboxylate groups of two glutamate residues, and by an aspartate residue [PMID: 16227203, PMID: 11301020, PMID: 12037559].
RCK domains occur in at least five different contexts:
- As a single domain on the C terminus of some K+ channels (for example, many prokaryotic K+ channels).
- As two tandem RCK domains on the C terminus of some transporters that form gating rings (for example, eukaryotic BK channels). The gating ring has an arrangement of eight identical RCK domains, one from each of the four pore-forming subunits and four from the intracellular solution.
- As two domains, one at the N terminus and another at the C terminus of transporter (for example, the prokaryotic trk system potassium uptake protein A).
- As a soluble protein (not part of a K+ channel) consisting of two tandem RCK domains.
- As a soluble protein consisting of a single RCK domain.
This entry represents the C-terminal subdomain of RCK.