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K + Channels

K + Channels. How do K + channel proteins achieve high selectivity and high throughput?. Selectivity: Rate K + /Rate Na + = 10,000 !. Radius K + = 1.5 Å Radius Na + = 1.1 Å. Throughput: 10 8 ions/second. Doyle et al (1998) Science 280, 69-77. Doyle et al (1998) Science 280, 69-77.

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K + Channels

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  1. K+ Channels How do K+ channel proteins achieve high selectivity and high throughput? Selectivity: Rate K+/Rate Na+ = 10,000 ! Radius K+ = 1.5 Å Radius Na+ = 1.1 Å Throughput: 108 ions/second

  2. Doyle et al (1998) Science 280, 69-77.

  3. Doyle et al (1998) Science 280, 69-77.

  4. 180 G77 (41, 57)  Y78 (-55, 39) G79 (100, 12)  -180 180

  5. Taken from Dianne Papazian

  6. K+ ions passing through selectivity filter Zhou et al., Nature, 414, 43, (2001)

  7. Taken from Dianne Papazian

  8. Doyle et al Science 280, 69-77 (1998)

  9. d - d - d - d - d + d + d + Helix Dipole Net negative charge Net positive charge

  10. + + - - A water-filled cavity and the pore helix dipole stabilize an ion in the middle of the membrane. Doyle et al., Science 280, 69-77 (1998) .

  11. Roux and Mackinnon, Science ,285:100-2 (1999)

  12. All K+ binding sites in selectivity filter can not be occupied at once due to electrostatic repulsion. Zhou et al., Nature, 414, 43, (2001)

  13. High flux due to ion repulsion that weakens binding pore Miller, Nature, 414, 23 (2001) Model from Cabral et al, Nature, 414, 37 (2001)

  14. Glycerol Channel (GlpF) from E. coli • Transports glycerol and some other alditols • Transports water (related to water channels) • Excludes ions, most notably H+

  15. The Structure Glycerols in channel A tetramer with four independent channels Fu et al., Science, 290:481 (2000)

  16. Side view of monomer G1, G2 and G3 are three glycerol molecules seen in the channel Fu et al., Science, 290:481 (2000)

  17. Topology Diagram of GlpF Channel Note two half TM helices than meet in the middle of the membrane Fu et al., Science, 290:481 (2000)

  18. What does glycerol look like? Hydrophobic surface Hydrophilic surface

  19. GlpF selectivity filter Hydrophobic surface Hydrophillic surface Fu et al., Science, 290:481 (2000)

  20. Specific for ampiphilic alditols Black bars: transport without GlpF Gray bars: transport with GlpF Fu et al., Science, 290:481 (2000)

  21. GlpF can also transport water. How does it exclude protons???

  22. O O O O H H H H H H H H Why doesn’t a proton wire form? H+

  23. + + - - Water passing through GlpF channel

  24. - - - - - - + + + + + + • A particular orientation of water is favored in the channel that is unfavorable for proton capture or release. Water orientation is favored by: • H-bonding groups in the channel • Helix dipoles

  25. Aspartate Transporter transports 1 Asp and 2 Na+

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