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UCSD BIBC 100 - K-channel Structure

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1K-channel structureIon selectivity explainedCox, Lehninger Principles in Biochemistry, chapter 12, figure 23Channels and transporters act as enzymes lowering the activationenergy for polar solutes diffusing across non-polar membranes2Voltage gated subunitS5-S6 pore liningS4 voltage sensorNon-voltage gated subunitS1-S2 pore liningSee also: Figure 20-31 Predicted secondary structure and membrane orientation of voltage-gated K+ channels.Cox, Lehninger Principles in Biochemistry, chapter 12, figure 38X-ray structure of bacterial K-channel KcsA tetramerSide view Top view3D.A. Doyle et al., Science, 1998, 280:69-77. Figure 20-16b X-Ray structure of the KcsA K+ channel. (right) A cutaway diagram viewed showing polar (red) and non-polar (yellow) pore lining residues. (left) KcsA tetramer with surface rendering of internal pore volume.Voet and Voet, Biochemistry, chapter 20Fab attachment and crystal packing of K-channel at 2Å resolutionTwo subunits and attached Fab fragments viewed perpendicular to the four-fold axis. The transmembrane outer and inner helices are labelled. The asterisk denotes the location of the central cavity, below the selectivity filter (red). Zhou et al., 2001, Nature 414:434D.A. Doyle et al., Science, 1998, 280:69-77. & Zhou et al., 2001, Nature 414:43Figure 20-17a Portions of the KcsA K+ channel responsible for its ion selectivity viewed similarly to Fig. 20-16. (a) The X-ray structure of the residues.“permanent” ion positions in selectivity filter (GYG) and central cavity regionK+ions (green spheres) along the ion pathway, and water molecules (red spheres) in the vicinityVoet and Voet, Biochemistry, chapter 20Ch Miller., 2001, Nature 414:23Permeation of K+ions through the pore of a K-channelThere are seven main sites for ions along the pore axis: one in the pore cavity, four in the selectivity filter (see structure below) and two just beyond the external end of the pore. The cavity site is fully occupied, but (as indicated in b) only half of the remaining six are occupied at any one time5K-selectivity and Na exclusion in K-channel, Nature Medicine, 1999Cation - oxygen coordination and dehydration energy penalty for Na+In hydration shellIn selectivity filterNa+channel topology and voltage gating mechanisms6Cox, Lehninger Principles in Biochemistry, chapter 12, figure 40Topology diagram of a voltage gated Na-channelDomains I through IV correspond to the 4 K-channel subunitsCox, Lehninger Principles in Biochemistry, chapter 12, figure 40Na-channel structure7Na-channel recording Open probability plotVoltage dependent gating of a Na-channelW. A. Catterall, 1988, Science


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