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Contact details

Georgios A. Spyroulias, PhD.
Department of Pharmacy
University of Patras
Panepistimioupoli-Rion,
GR-26504 Patras, GREECE
Tel:    +30.2610.969950 (office)
+30.2610.969951 (terra silico)
+30.2610.969952 (terra vitro)
Fax:    +30.2610.969950
Email:  G.A.Spyroulias@upatras.gr

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Now is: 2017-09-20 07:31
Small conductance Ca(2+)-activated K(+) channels
Small-conductance Ca2+-activated potassium (SK) channels are K+ channels with six transmembrane domains that open only upon a rise in intracellular Ca2+ to submicromolar concentrations. Under physiological conditions, Ca2+ is provided by co-localized Ca2+-sources such as voltage- or ligand-gated Ca2+ channels. Once activated by Ca2+, SK channels are responsible for the slow afterhyperpolarization that follows the action potential in many types of central neurons, controls their firing pattern and therefore is essential for normal neurotransmission. The high-affinity Ca2+-gating of SK channels is unique among K+-channels and is achieved by the use of calmodulin (CaM), an ubiquitously expressed EF-hand protein, as a Ca2+-sensor. The C-terminal globular domain of CaM is constitutively associated with the so-called calmodulin binding domain (CaMBD) of the SK subunit. Ca2+ binding to the EF-hands in the N-terminal domain of CaM promotes Ca2+-dependent interactions between the CaMBD and CaM that trigger the opening of the channel pore.
The unbound CaMBD consists of highly flexible N- and C-termini flanking a short helical core region between residues 423-437 which is essential for the tight constitutive association of CaMBD with Ca2+-free CaM. The crystallized complex of CaMBD, CaM and Ca2+ presents as a CaMBD dimer with a CaM molecule bound at each end. NMR experiments on the Ca2+-free complex confirmed that Ca2+-free interactions between CaM and CaMBD occur only at the C-terminal globular domain of CaM.
Our studies focused on the solution NMR studies on a minimal complex consisting of the C-terminal domain of CaM and a synthetic 23-residue peptide corresponding to the CaMBD core region. The reduction in size of the binding partners diminished the previously observed exchange equilibrium and allowed an exact mapping of the protein-protein interaction in the absence of Ca2+.  The CaM-sk2 peptide complex has been reconstituted through titration studies and an NMR-driven docking approach using chemical shift perturbation data.