Regulators 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).
[4][3][1]. 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
[4]. Some have a conserved sequence motif
(G-x-G-x-x-G-x(n)-[DE]) for NAD+ binding
[5], 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
sulfate, sodium and other transporters.
The X-ray structure of several RCK domains has been solved (see for example
{PDB:1LNQ})
[2][3][1]. 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) subdomains. The RCK-N subdomain forms a Rossmann fold with two alpha
helices (alpha A and alpha B) on one side of a six stranded parallel beta
sheet (beta A to beta F) and three alpha helices (alpha C, alpha D and alpha
E) on the other side. The RCK-C subdomain is an all-beta-strand fold. It forms
an extention of the dimer interface and further stabilizes the RCK homodimer
[2][3][1]. 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
[2][3][1].
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.
We developed two profiles for this domain, one that spans the RCK-N subdomain
and the other which covers the RCK-C subdomain.