1887

Chapter 4 : The Molecular Basis of K Channel Gating

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

The Molecular Basis of K Channel Gating, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816452/9781555813284_Chap04-1.gif /docserver/preview/fulltext/10.1128/9781555816452/9781555813284_Chap04-2.gif

Abstract:

Until recently, electrophysiology served as an indirect window into one's understanding of channel gating and structure. A clearer picture of protein movements involved in gating has recently emerged from the merger of crystallographic and spectroscopic studies with functional analysis. These and other emerging results are discussed from the perspective that understanding the molecular process in details of gating helps explain how a wide variety of effectors can function to open or close a target channel, allowing for the large diversity of channels. A large helix opening may not be a requirement for channel gating as a small helix bend can allow K ions an adequate path for flow. The cytoplasmic gating ring of the channel is formed by an octamer of RCK domains. The mechanism of channel gating lies at the core of one's understanding of how channels respond to specific stimuli. Information extracted from functional, crystallographic, and spectroscopic studies of prokaryotic channels has revealed molecular details of how the inner helices and the selectivity filter are involved in channel gating. Focusing the gating forces at a consistent position along the ion conduction pathway allows channels to exist with a large diversity of regulatory domains but maintain a conserved core architecture necessary for efficient function.

Citation: Ptak C, Liu Y, Perozo E. 2005. The Molecular Basis of K Channel Gating, p 69-81. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch4

Key Concept Ranking

Amino Acids
0.7339185
Membrane Protein
0.5125326
Escherichia coli
0.5009773
Ion Channels
0.5003906
0.7339185
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1.
Figure 1.

Inner helix bending motion. (A) A single inner helix from the four known K channel structures (closed: KcsA, black; KirBac, dark gray; open: MthK, gray; KvAP, white) was aligned from the selectivity filter to the glycine hinge. The opposite KcsA inner helix is shown to provide the relative position of the bending helix within the tetramer. (B) A top view of the separation of inner transmembrane helices. (C) Cα-Cα?distances for residues along the inner helices of K channel structures provide an idea of the size of the ion conduction pathway. Major differences between open and closed channels occur after the glycine hinge.the rigidness of the whole helix has been shown by recent crystal structures to be broken at a glycine hinge point (equivalent to G99 in KcsA). Nevertheless, the specific details of the separation of the inner helices measured by EPR are a good representation of the movements involved in KcsA gating. In a complementary experiment using site-directed mass tagging of pore-lining residues in KcsA, an increase in cysteine residue accessibility to methanethiosulfonate reagents was observed at lower pH values ( ).

Citation: Ptak C, Liu Y, Perozo E. 2005. The Molecular Basis of K Channel Gating, p 69-81. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

MthK gating movements. Ligand-induced conformational changes in the cytoplasmic gating ring control the open state of MthK. A structural alignment (MthK-Ca, black; KtnBsu-nad, dark gray; Kch-empty, gray; KtnBsu-nadh, white) of the hinge between the RCK domain and the peripheral domain provides insight into the physical movements within the cytoplasmic domain dimer that occur in response to the release of ligand.

Citation: Ptak C, Liu Y, Perozo E. 2005. The Molecular Basis of K Channel Gating, p 69-81. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816452.chap4
1. Anantharaman, V.,, E. V. Koonin,, and L. Aravind. 2001. Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains. J. Mol. Biol. 307:12711292.
2. Borbat, P. P.,, H. S. McHaourab,, and J. H. Freed. 2002. Protein structure determination using long-distance constraints from double-quantum coherence ESR: study of T4 lysozyme. J. Am. Chem. Soc. 124:53045314.
3. Cornette, J. L.,, K. B. Cease,, H. Margalit,, J. L. Spouge,, J. A. Berzofsky,, and C. DeLisi. 1987. Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. J. Mol. Biol. 195: 659685.
4. Cortes, D. M.,, L. G. Cuello,, and E. Perozo. 2001. Molecular architecture of full-length KcsA: role of cytoplasmic domains in ion permeation and activation gating. J. Gen. Physiol. 117:165180.
5. Cortes, D. M.,, and E. Perozo. 1997. Structural dynamics of the Streptomyces lividans K+ channel (SKC1): oligomeric stoichiometry and stability. Biochemistry 36:1034310352.
6. Cox, D. H.,, and R. W. Aldrich. 2000. Role of the beta1 subunit in large-conductance Ca2+-activated K+ channel gating energetics. Mechanisms of enhanced Ca2+ sensitivity. J. Gen. Physiol. 116:411432.
7. Cuello, L. G.,, J. G. Romero,, D. M. Cortes,, and E. Perozo. 1998. pH-dependent gating in the Streptomyces lividans K+ channel. Biochemistry 37:32293236.
8. Cui, J.,, and R. W. Aldrich. 2000. Allosteric linkage between voltage and Ca2+-dependent activation of BK-type mslo1 K+channels . Biochemistry 39:1561215619.
9. del Camino, D.,, M. Holmgren,, Y. Liu,, and G. Yellen. 2000. Blocker protection in the pore of a voltage-gated K+ channel and its structural implications. Nature 403:321325.
10. Doyle, D. A.,, J. Morais Cabral,, R. A. Pfuetzner,, A. Kuo,, J. M. Gulbis,, S. L. Cohen,, B. T. Chait,, and R. MacKinnon. 1998. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:6977.
11. Farahbakhsh, Z. T.,, C. Altenbach,, and W. L. Hubbell. 1992. Spin labeled cysteines as sensors for protein-lipid interaction and conformation in rhodopsin. Photochem. Photobiol. 56:10191033.
12. Gibrat, J. F.,, T. Madej,, and S. H. Bryant. 1996. Surprising similarities in structure comparison. Curr. Opin. Struct. Biol. 6:377385.
13. Gross, A.,, L. Columbus,, K. Hideg,, C. Altenbach,, and W. L. Hubbell. 1999. Structure of the KcsA potassium channel from Streptomyces lividans: a site-directed spin labeling study of the second transmembrane segment. Biochemistry 38:1032410335.
14. Gulbis, J. M.,, and D. A. Doyle. 2004. Potassium channel structures: do they conform? Curr. Opin. Struct. Biol. 14:440446.
15. Heginbotham, L.,, L. Kolmakova-Partensky,, and C. Miller. 1998. Functional reconstitution of a prokaryotic K+ channel. J. Gen. Physiol. 111:741749.
16. Heginbotham, L.,, M. LeMasurier,, L. Kolmakova-Partensky,, and C. Miller. 1999. Single Streptomyces lividans K+ channels: functional asymmetries and sidedness of proton activation. J. Gen. Physiol. 114: 551560.
17. Hellmer, J.,, and C. Zeilinger. 2003. MjK1, a K+ channel from M. jannaschii, mediates K+ uptake and K+ sensitivity in E. coli. FEBS Lett. 547:165169.
18. Hilgemann, D. W.,, and R. Ball. 1996. Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2. Science 273:956959.
19. Hilgemann, D. W.,, S. Feng,, and C. Nasuhoglu. 2001. The complex and intriguing lives of PIP2 with ion channels and transporters. Sci. STKE 2001:RE19.
20. Horrigan, F. T.,, and R. W. Aldrich. 2002. Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels. J. Gen. Physiol. 120:267305.
21. Hu, L.,, J. Shi,, Z. Ma,, G. Krishnamoorthy,, F. Sieling,, G. Zhang,, F. T. Horrigan,, and J. Cui. 2003. Participation of the S4 voltage sensor in the Mg2+-dependent activation of large conductance (BK) K+ channels. Proc. Natl. Acad. Sci. USA 100:1048810493.
22. Huang, C. L.,, S. Feng,, and D. W. Hilgemann. 1998. Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by G+ . Nature 391:803806.
23. Hubbell, W. L.,, A. Gross,, R. Langen,, and M. A. Lietzow. 1998. Recent advances in site-directed spin labeling of proteins. Curr. Opin. Struct. Biol. 8:649656.
24. Hung, A. Y.,, and M. Sheng. 2002. PDZ domains: structural modules for protein complex assembly. J. Biol. Chem. 277:56995702.
25. Hustedt, E. J.,, A. I. Smirnov,, C. F. Laub,, C. E. Cobb,, and A. H. Beth. 1997. Molecular distances from dipolar coupled spin-labels: the global analysis of multifrequency continuous wave electron paramagnetic resonance data. Biophys. J. 72:18611877.
26. Im, Y. J.,, J. H. Lee,, S. H. Park,, S. J. Park,, S. H. Rho,, G. B. Kang,, E. Kim,, and S. H. Eom. 2003. Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization. J. Biol. Chem. 278:4809948104.
27. Jiang, Y.,, A. Lee,, J. Chen,, M. Cadene,, B. T. Chait,, and R. MacKinnon. 2002. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417:515522.
28. Jiang, Y.,, A. Lee,, J. Chen,, V. Ruta,, M. Cadene,, B. T. Chait,, and R. MacKinnon. 2003a. X-ray structure of a voltage-dependent K+ channel. Nature 423:3341.
29. Jiang, Y.,, A. Pico,, M. Cadene,, B. T. Chait,, and R. MacKinnon. 2001. Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel. Neuron 29:593601.
30. Jiang, Y.,, V. Ruta,, J. Chen,, A. Lee,, and R. MacKinnon. 2003b. The principle of gating charge movement in a voltage-dependent K+ channel. Nature 423:4248.
31. Jin, T.,, L. Peng,, T. Mirshahi,, T. Rohacs,, K. W. Chan,, R. Sanchez,, and D. E. Logothetis. 2002. The βγsubunits of G proteins gate a K+ channel by pivoted bending of a transmembrane segment. Mol. Cell 10:469481.
32. Jones, B. E.,, P. Rajagopal,, and R. E. Klevit. 1997. Phosphorylation on histidine is accompanied by localized structural changes in the phosphocarrier protein, HPr from Bacillus subtilis. Protein. Sci. 6:21072119.
33. Kelly, B. L.,, and A. Gross. 2003. Potassium channel gating observed with site-directed mass tagging. Nat. Struct. Biol. 10:280284.
Kuo, A.,, J. M. Gulbis,, J. F. Antcliff,, T. Rahman,, E. D. Lowe,, J. Zimmer,, J. Cuthbertson,, F. M. Ashcroft,, T. Ezaki,, and D. A. Doyle. 2003.a. Crystal structure of the potassium channel KirBac1.1 in the closed state. Science 300:19221926.
35. Kuo, M. M.,, Y. Saimi,, and C. Kung. 2003b. Gain-of-function mutations indicate that Escherichia coli Kch forms a functional K+ conduit in vivo. EMBO J. 22:40494058.
36. Labro, A. J.,, A. L. Raes,, I. Bellens,, N. Ottschytsch,, and D. J. Snyders. 2003. Gating of shaker-type channels requires the flexibility of S6 caused by prolines. J. Biol. Chem. 278:5072450731.
37. Liu, Y.,, M. Holmgren,, M. E. Jurman,, and G. Yellen. 1997. Gated access to the pore of a voltage-dependent K+ channel. Neuron 19:175184.
38. Liu, Y. S.,, P. Sompornpisut,, and E. Perozo. 2001. Structure of the KcsA channel intracellular gate in the open state. Nat. Struct. Biol. 8:883887.
39. Magidovich, E.,, and O. Yifrach. 2004. Conserved gating hinge in ligand- and voltage-dependent K+ channels. Biochemistry 43:1324213247.
40. Magleby, K. L. 2003. Gating mechanism of BK (Slo1) channels: so near, yet so far. J. Gen. Physiol. 121:8196.
41. McHaourab, H. S.,, M. A. Lietzow,, K. Hideg,, and W. L. Hubbell. 1996. Motion of spin-labeled side chains in T4 lysozyme. Correlation with protein structure and dynamics. Biochemistry 35:76927704.
42. McHaourab, H. S.,, K. J. Oh,, C. J. Fang,, and W. L. Hubbell. 1997. Conformation of T4 lysozyme in solution. Hinge-bending motion and the substrate-induced conformational transition studied by site-directed spin labeling. Biochemistry 36:307316.
43. Molina, M. L.,, J. A. Encinar,, F. N. Barrera,, G. Fernandez-Ballester,, G. Riquelme,, and J. M. Gonzalez-Ros. 2004. Influence of C-terminal protein domains and protein-lipid interactions on tetramerization and stability of the potassium channel KcsA. Biochemistry 43:1492414931.
44. Niu, X.,, X. Qian,, and K. L. Magleby. 2004. Linker-gating ring complex as passive spring and Ca2+-dependent machine for a voltage- and Ca2+-activated potassium channel. Neuron 42:745756.
45. Perozo, E.,, D. M. Cortes,, and L. G. Cuello. 1998. Three-dimensional architecture and gating mechanism of a K+ channel studied by EPR spectroscopy. Nat. Struct. Biol. 5:459469.
46. Perozo, E.,, D. M. Cortes,, and L. G. Cuello. 1999. Structural rearrangements underlying K+-channel activation gating. Science 285:7378.
47. Ptak, C. P.,, L. G. Cuello,, and E. Perozo. 2005. Electrostatic interaction of a K+ channel RCK domain with charged membrane surfaces. Biochemistry 44:6271.
48. Rabenstein, M. D.,, and Y. K. Shin. 1995. Determination of the distance between two spin labels attached to a macromolecule. Proc. Natl. Acad. Sci. USA 92:82398243.
49. Roosild, T. P.,, S. Miller,, I. R. Booth,, and S. Choe. 2002. A mechanism of regulating transmembrane potassium flux through a ligand-mediated conformational switch. Cell 109:781791.
50. Shi, J.,, G. Krishnamoorthy,, Y. Yang,, L. Hu,, N. Chaturvedi,, D. Harilal,, J. Qin,, and J. Cui. 2002. Mechanism of magnesium activation of calcium-activated potassium channels. Nature 418:876880.
51. Sompornpisut, P.,, Y.-S. Liu,, and E. Perozo. 2001. Calculation of rigid-body conformational changes using restraint-driven cartesian transformations. Biophys. J. 81:25302546.
52. Waygood, E. B. 1998. The structure and function of HPr. Biochem. Cell Biol. 76:359367.
53. Webster, S. M.,, D. Del Camino,, J. P. Dekker,, and G. Yellen. 2004. Intracellular gate opening in Shaker K+ channels defined by high-affinity metal bridges. Nature 428:864868.
54. Xia, X. M.,, X. Zeng,, and C. J. Lingle. 2002. Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature 418:880884.
55. Yi, B. A.,, Y. F. Lin,, Y. N. Jan,, and L. Y. Jan. 2001. Yeast screen for constitutively active mutant G proteinactivated potassium channels. Neuron 29:657667.
56. Zhao, Y.,, V. Yarov-Yarovoy,, T. Scheuer,, and W. A. Catterall. 2004. A gating hinge in Na+ channels; a molecular switch for electrical signaling. Neuron 41:859865.
57. Zhou, Y.,, J. H. Morais-Cabral,, A. Kaufman,, and R. MacKinnon. 2001. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution. Nature 414:4348.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error