Home LiteratureArticle Details
PMID: 17703190 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Crystal structure of a Kir3.1-prokaryotic Kir channel chimera.

The EMBO journal ·Vol. 26 ·No. 17 ·2007-09-05 ·Pages 4005-15

Nishida M, Cadene M, Chait BT, MacKinnon R

Abstract

The Kir3.1 K(+) channel participates in heart rate control and neuronal excitability through G-protein and lipid signaling pathways. Expression in Escherichia coli has been achieved by replacing three fourths of the transmembrane pore with the pore of a prokaryotic Kir channel, leaving the cytoplasmic pore and membrane interfacial regions of Kir3.1 origin. Two structures were determined at 2.2 A. The selectivity filter is identical to the Streptomyces lividans K(+) channel within error of measurement (r.m.s.d.<0.2 A), suggesting that K(+) selectivity requires extreme conservation of three-dimensional structure. Multiple K(+) ions reside within the pore and help to explain voltage-dependent Mg(2+) and polyamine blockade and strong rectification. Two constrictions, at the inner helix bundle and at the apex of the cytoplasmic pore, may function as gates: in one structure the apex is open and in the other, it is closed. Gating of the apex is mediated by rigid-body movements of the cytoplasmic pore subunits. Phosphatidylinositol 4,5-biphosphate-interacting residues suggest a possible mechanism by which the signaling lipid regulates the cytoplasmic pore.

MeSH Terms
Amino Acid Sequence Bacterial Proteins/genetics Binding Sites Burkholderia/metabolism Crystallography, X-Ray Escherichia coli/metabolism G Protein-Coupled Inwardly-Rectifying Potassium Channels/biosynthesis,chemistry,genetics Ion Channel Gating Models, Molecular Molecular Sequence Data Protein Conformation Recombinant Fusion Proteins/biosynthesis,chemistry,genetics
Chemicals
Bacterial Proteins G Protein-Coupled Inwardly-Rectifying Potassium Channels Recombinant Fusion Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nishida Motohiko
Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065, USA.
Cadene Martine
Chait Brian T
MacKinnon Roderick
References (62)
62 references, click to expand
  1. Identification of a potassium channel site that interacts with G protein betagamma subunits to mediate agonist-induced signaling.
    J Biol Chem. 1999 Apr 30;274(18):12517-24 PMID: 10212228
  2. Regulation of ROMK1 channel by protein kinase A via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism.
    Proc Natl Acad Sci U S A. 1999 May 11;96(10):5820-5 PMID: 10318968
  3. Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.
    Nat Cell Biol. 1999 Jul;1(3):183-8 PMID: 10559906
  4. Structural determinants of PIP(2) regulation of inward rectifier K(ATP) channels.
    J Gen Physiol. 2000 Nov;116(5):599-608 PMID: 11055989
  5. Yeast screen for constitutively active mutant G protein-activated potassium channels.
    Neuron. 2001 Mar;29(3):657-67 PMID: 11301025
  6. Coupling Gbetagamma-dependent activation to channel opening via pore elements in inwardly rectifying potassium channels.
    Neuron. 2001 Mar;29(3):669-80 PMID: 11301026
  7. Phospholipids as modulators of K(ATP) channels: distinct mechanisms for control of sensitivity to sulphonylureas, K(+) channel openers, and ATP.
    Mol Pharmacol. 2001 May;59(5):1086-93 PMID: 11306691
  8. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.
    Cell. 2001 May 18;105(4):511-9 PMID: 11371347
  9. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.
    Nature. 2001 Nov 1;414(6859):43-8 PMID: 11689936
  10. The complex and intriguing lives of PIP2 with ion channels and transporters.
    Sci STKE. 2001 Dec 04;2001(111):re19 PMID: 11734659
  11. A family of putative Kir potassium channels in prokaryotes.
    BMC Evol Biol. 2001;1:14 PMID: 11806753
  12. Structural determinants and specificities for ROMK1-phosphoinositide interaction.
    Am J Physiol Renal Physiol. 2002 May;282(5):F826-34 PMID: 11934692
  13. Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
    Neuron. 2002 Jun 13;34(6):933-44 PMID: 12086641
  14. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome).
    J Clin Invest. 2002 Aug;110(3):381-8 PMID: 12163457
  15. Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0.
    Rev Physiol Biochem Pharmacol. 2002;145:47-179 PMID: 12224528
  16. Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
    Cell. 2002 Dec 27;111(7):957-65 PMID: 12507423
  17. Phosphatidylinositol 4,5-bisphosphate (PIP2) modulation of ATP and pH sensitivity in Kir channels. A tale of an active and a silent PIP2 site in the N terminus.
    J Biol Chem. 2003 Mar 21;278(12):10500-5 PMID: 12514171
  18. A threonine residue (Thr71) at the intracellular end of the M1 helix plays a critical role in the gating of Kir6.2 channels by intracellular ATP and protons.
    J Membr Biol. 2003 Mar 15;192(2):111-22 PMID: 12682799
  19. Crystal structure of the potassium channel KirBac1.1 in the closed state.
    Science. 2003 Jun 20;300(5627):1922-6 PMID: 12738871
  20. Mapping the Gbetagamma-binding sites in GIRK1 and GIRK2 subunits of the G protein-activated K+ channel.
    J Biol Chem. 2003 Aug 1;278(31):29174-83 PMID: 12743112
  21. Contribution of cytosolic cysteine residues to the gating properties of the Kir2.1 inward rectifier.
    Biophys J. 2003 Jun;84(6):3717-29 PMID: 12770878
  22. Defective potassium channel Kir2.1 trafficking underlies Andersen-Tawil syndrome.
    J Biol Chem. 2003 Dec 19;278(51):51779-85 PMID: 14522976
  23. Interaction mechanisms between polyamines and IRK1 inward rectifier K+ channels.
    J Gen Physiol. 2003 Nov;122(5):485-500 PMID: 14581581
  24. The occupancy of ions in the K+ selectivity filter: charge balance and coupling of ion binding to a protein conformational change underlie high conduction rates.
    J Mol Biol. 2003 Nov 7;333(5):965-75 PMID: 14583193
  25. betaL-betaM loop in the C-terminal domain of G protein-activated inwardly rectifying K(+) channels is important for G(betagamma) subunit activation.
    J Physiol. 2004 Mar 16;555(Pt 3):643-57 PMID: 14724209
  26. Mechanism of rectification in inward-rectifier K+ channels.
    Annu Rev Physiol. 2004;66:103-29 PMID: 14977398
  27. Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators.
    J Biol Chem. 2004 Sep 3;279(36):37271-81 PMID: 15155739
  28. The CCP4 suite: programs for protein crystallography.
    Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3 PMID: 15299374
  29. Molecular diversity and regulation of renal potassium channels.
    Physiol Rev. 2005 Jan;85(1):319-71 PMID: 15618483
  30. Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit.
    EMBO J. 2005 Jan 26;24(2):229-39 PMID: 15650751
  31. Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification.
    Nat Neurosci. 2005 Mar;8(3):279-87 PMID: 15723059
  32. Signal transduction pathway for the substance P-induced inhibition of rat Kir3 (GIRK) channel.
    J Physiol. 2005 Apr 15;564(Pt 2):489-500 PMID: 15731196
  33. Mechanism of the voltage sensitivity of IRK1 inward-rectifier K+ channel block by the polyamine spermine.
    J Gen Physiol. 2005 Apr;125(4):413-26 PMID: 15795311
  34. A gating mutation at the internal mouth of the Kir6.2 pore is associated with DEND syndrome.
    EMBO Rep. 2005 May;6(5):470-5 PMID: 15864298
  35. Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy.
    Diabetes. 2005 Sep;54(9):2503-13 PMID: 16123337
  36. ATP-sensitive K+ channels: regulation of bursting by the sulphonylurea receptor, PIP2 and regions of Kir6.2.
    J Physiol. 2006 Mar 1;571(Pt 2):303-17 PMID: 16373383
  37. K(ATP) channels and insulin secretion: a key role in health and disease.
    Biochem Soc Trans. 2006 Apr;34(Pt 2):243-6 PMID: 16545085
  38. Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK) potassium channel.
    EMBO Rep. 2006 Jun;7(6):611-6 PMID: 16641935
  39. Andersen's syndrome mutation effects on the structure and assembly of the cytoplasmic domains of Kir2.1.
    Biochemistry. 2006 Jul 18;45(28):8599-606 PMID: 16834334
  40. Localization of the pH gate in Kir1.1 channels.
    Biophys J. 2006 Oct 15;91(8):2901-9 PMID: 16891366
  41. An andersen-Tawil syndrome mutation in Kir2.1 (V302M) alters the G-loop cytoplasmic K+ conduction pathway.
    J Biol Chem. 2007 Feb 23;282(8):5781-9 PMID: 17166852
  42. Structural and thermodynamic properties of selective ion binding in a K+ channel.
    PLoS Biol. 2007 May;5(5):e121 PMID: 17472437
  43. The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart.
    Nature. 1987 Jan 22-28;325(6102):321-6 PMID: 2433589
  44. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+.
    Nature. 1987 Jan 8-14;325(7000):156-9 PMID: 2433601
  45. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2560-4 PMID: 2436236
  46. Processing of X-ray diffraction data collected in oscillation mode.
    Methods Enzymol. 1997;276:307-26 PMID: 27754618
  47. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
    Science. 1995 Apr 21;268(5209):423-6 PMID: 7716547
  48. Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel.
    Neuron. 1995 May;14(5):1047-54 PMID: 7748552
  49. The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.
    Nature. 1995 Mar 9;374(6518):135-41 PMID: 7877685
  50. Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification.
    Nature. 1994 Nov 24;372(6504):366-9 PMID: 7969496
  51. Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
    Nature. 1994 Jul 14;370(6485):143-6 PMID: 8022483
  52. Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel.
    Nature. 1994 Mar 17;368(6468):255-7 PMID: 8145826
  53. Specification of pore properties by the carboxyl terminus of inwardly rectifying K+ channels.
    Science. 1994 May 6;264(5160):844-7 PMID: 8171340
  54. Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
    Science. 1996 Aug 16;273(5277):956-9 PMID: 8688080
  55. Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.
    Nat Genet. 1996 Oct;14(2):152-6 PMID: 8841184
  56. Anionic phospholipids activate ATP-sensitive potassium channels.
    J Biol Chem. 1997 Feb 28;272(9):5388-95 PMID: 9038137
  57. Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
    Nature. 1998 Feb 19;391(6669):803-6 PMID: 9486652
  58. The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
    Science. 1998 Apr 3;280(5360):69-77 PMID: 9525859
  59. Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
    J Gen Physiol. 1998 Sep;112(3):333-49 PMID: 9725893
  60. Crystallography & NMR system: A new software suite for macromolecular structure determination.
    Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 PMID: 9757107
  61. Membrane phospholipid control of nucleotide sensitivity of KATP channels.
    Science. 1998 Nov 6;282(5391):1138-41 PMID: 9804554
  62. PIP2 and PIP as determinants for ATP inhibition of KATP channels.
    Science. 1998 Nov 6;282(5391):1141-4 PMID: 9804555
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601828
Published
2007-09-05
Epub
2007-00-16
Pages
4005-15
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1994128
Subset
IM
Grants
NCRR NIH HHS · P41 RR000862 · United States
NIGMS NIH HHS · R01 GM043949 · United States
NIGMS NIH HHS · GM 43949 · United States
NCRR NIH HHS · RR 00862 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7601828 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2