Voltage-Activated K+ Channels

Voltage-gated K+ channels are transmembrane proteins that control and regulate the flow of K+ ions across cell membranes in response to changes in membrane potential and are essential for the propagation of action potentials in the nervous system. Detailed 3d structures are required in order to address the function of those channels. Available experimental results provide specific constraints on the structure of the channel, even though the direct translation of all the available information into 3d structures is not trivial. Computational methods are being used to refine structural models of the voltage-activated K+ channels.

Why are the models evolving with time? The simple answer is that it has been possible to better define the structures as more data has become available. In the following paragraph, a brief history of the models is given:

Our very first efforts mostly showed that there was insufficient experimental restraints to construct models with reasonable confidence (Roux, 2002). The subsequence models (Silverman et al, 2003; Laine et al 2003), were better constrained, but still uncertain due to lack of data. In our last efforts, we constructed molecular models of the Shaker K+ channel in the open and the closed state using the x-ray structure of the bacterial channel KvAP, together with all available experimental data (Chanda et al, 2005). Three months after submission of the manuscript (April 2005), the structure of the Kv1.2 channel determined by x-ray crystallography was published (Long et al, 2005). Though there clearly some structural differences, the main structural features of the latest model (Chanda et al, 2005), which was developed on the basis of a wide range of structural, functional and biophysical experiments, are in are in excellent agreement with the x-ray structure of the Kv1.2 channel (Long et al, 2005).

Comparison of the Kv1.2 x-ray structure and the model of Shaker .

Download the Shaker-Agitoxin model based on Laine et al (2003) and Eriksson and Roux (2002) (pdb format)

Download the Shaker open state model of Chanda et al (2005) (pdb format)

Download the Shaker closed state model of Chanda et al (2005) (pdb format)


B ROUX. "What can be deduced about the structure of Shaker from available data?" in "Ion channels: From atomic resolution physiology to functional genomics", Novartis Foundation Symposium 245, pp. 84-101, G. Bock Editor, John Wiley & Sons Ltd., Chichester (2002). [ pdf ]

W.R. SILVERMAN, B. ROUX and D.M. PAPAZIAN, "Structural basis of two-stage voltage-dependent activation in K+ channels", Proc. Nat. Acad. Sci. 100, 2935-2940 (2003). [ pdf ]

M. LAINE, M.C.A. LIN, J.A. BANNISTER, W.R. SILVERMAN, B. ROUX and D.M. PAPAZIAN, "Atomic proximity between S4 segment and pore domain in Shaker potassium channels", Neuron 39, 467-481 (2003). [ pdf ]

M. LAINE, D.M. PAPAZIAN and B.ROUX, "Critical assessment of a proposed model of Shaker", FEBS Lett. 564, 257-63 (2004). [ pdf ]

M.A.L. ERIKSSON and B. ROUX, "Modeling the structure of Agitoxin in complex with the Shaker K+ channel. A computational approach based on experimental distance restraints extracted from thermodynamic mutant cycles" Biophys. J. 83, 2595-2609 (2002). [ pdf ]

B. CHANDA, O. K. ASAMOAH, R. BLUNCK, B. ROUX, F. BEZANILLA, "Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement" Nature 436, 852-856 (2005). [ pdf ]