Volume 9 Issue 6
Jun.  2018
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Jing-Xiang Wu, Dian Ding, Mengmeng Wang, Yunlu Kang, Xin Zeng, Lei Chen. Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels[J]. Protein&Cell, 2018, 9(6): 553-567. doi: 10.1007/s13238-018-0530-y
Citation: Jing-Xiang Wu, Dian Ding, Mengmeng Wang, Yunlu Kang, Xin Zeng, Lei Chen. Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels[J]. Protein&Cell, 2018, 9(6): 553-567. doi: 10.1007/s13238-018-0530-y

Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels

doi: 10.1007/s13238-018-0530-y

The work is supported by grants from the Ministry of Science and Technology of China (National Key R&D Program of China, 2016YFA0502004 to Lei Chen) and National Natural Science Foundation of China (Grant Nos. 31622021 and 31521062 to Lei Chen) and Young Thousand Talents Program of China to Lei Chen and the China Postdoctoral Science Foundation (2016M600856 and 2017T100014 to Jing-Xiang Wu). Jing-Xiang Wu is supported by the postdoctoral foundation of the Peking-Tsinghua Center for Life Sciences, Peking University.

  • Received Date: 2018-03-06
  • Rev Recd Date: 2018-03-14
  • ATP-sensitive potassium channels (KATP) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic KATP channels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore important drug targets. Here, we present three structures of pancreatic KATP channels solved by cryoelectron microscopy (cryo-EM), at resolutions ranging from 4.1 to 4.5 Å. These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6.2 (inward-rectifying potassium channel 6.2) N-terminus participates in the coupling between the peripheral SUR1 (sulfonylurea receptor 1) subunit and the central Kir6.2 channel, reveal the binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP binding on nucleotide binding domains (NBDs) drives a conformational change of the SUR1 subunit.
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  • [1]
    Adams PD et al (2010) PHENIX:a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66:213-221
    Aguilar-Bryan L et al (1990) Photoaffinity labeling and partial purification of the beta cell sulfonylurea receptor using a novel, biologically active glyburide analog. J Biol Chem 265:8218-8224
    Aguilar-Bryan L et al (1995) Cloning of the beta cell high-affinity sulfonylurea receptor:a regulator of insulin secretion. Science 268:423-426
    Aittoniemi J et al (2009) Review. SUR1:a unique ATP-binding cassette protein that functions as an ion channel regulator. Philos Trans R Soc Lond B Biol Sci 364:257-267
    Ashcroft FM et al (2017) Neonatal diabetes and the KATP channel:from mutation to therapy. Trends Endocrinol Metab 28:377-387
    Babenko AP, Bryan J (2002) SUR-dependent modulation of KATP channels by an N-terminal KIR6.2 peptide. Defining intersubunit gating interactions. J Biol Chem 277:43997-44004
    Babenko AP et al (1999) The N-terminus of KIR6.2 limits spontaneous bursting and modulates the ATP-inhibition of KATP channels. Biochem Biophys Res Commun 255:231-238
    Bai XC et al (2015) Sampling the conformational space of the catalytic subunit of human gamma-secretase. Elife. https://doi.org/10.7554/eLife.11182
    Baukrowitz T et al (1998) PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282:1141-1144
    Bryan J et al (2005) Insulin secretagogues, sulfonylurea receptors and K(ATP) channels. Curr Pharm Des 11:2699-2716
    Carr RD et al (2003) NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat. Diabetes 52:2513-2518
    Chen S et al (2013) High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135:24-35
    Choi KH et al (2008) Testing for violations of microscopic reversibility in ATP-sensitive potassium channel gating. J Phys Chem B 112:10314-10321
    Clement JPT et al (1997) Association and stoichiometry of K(ATP) channel subunits. Neuron 18:827-838
    Devaraneni PK et al (2015) Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism. J Biol Chem 290:7980-7991
    Emsley P et al (2010) Features and development of coot. Acta Crystallogr D Biol Crystallogr 66:486-501
    Flagg TP et al (2010) Muscle KATP channels:recent insights to energy sensing and myoprotection. Physiol Rev 90:799-829
    Goehring A et al (2014) Screening and large-scale expression of membrane proteins in mammalian cells for structural studies. Nat Protoc 9:2574-2585
    Gribble FM et al (1997) The interaction of nucleotides with the tolbutamide block of cloned ATP-sensitive K+ channel currents expressed in Xenopus oocytes:a reinterpretation. J Physiol 504(Pt 1):35-45
    Hibino H et al (2010) Inwardly rectifying potassium channels:their structure, function, and physiological roles. Physiol Rev 90:291-366
    Hilgemann DW, Ball R (1996) Regulation of cardiac Na+, Ca2+ exchange and KATP potassium channels by PIP2. Science 273:956-959
    Hopkins WF et al (1992) Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic betacells and HIT cells. J Membr Biol 129:287-295
    Jones PM, George AM (2017) How intrinsic dynamics mediates the allosteric mechanism in the ABC transporter nucleotide binding domain dimer. J Chem Theory Comput 13:1712-1722
    Karpowich N et al (2001) Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter. Structure 9:571-586
    Kawate T, Gouaux E (2006) Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins. Structure 14:673-681
    Kimanius D et al (2016) Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2. Elife. https://doi.org/10.7554/eLife.18722
    Koster JC et al (1999) ATP inhibition of KATP channels:control of nucleotide sensitivity by the N-terminal domain of the Kir6.2 subunit. J Physiol 515(Pt 1):19-30
    Kuhner P et al (2012) Importance of the Kir6.2 N-terminus for the interaction of glibenclamide and repaglinide with the pancreatic K (ATP) channel. Naunyn Schmiedebergs Arch Pharmacol 385:299-311
    Lee KPK et al (2017) Molecular structure of human KATP in complex with ATP and ADP. Elife. https://doi.org/10.7554/eLife.32481
    Li N et al (2017) Structure of a pancreatic ATP-sensitive potassium channel. Cell 168:101-110
    Locher KP (2016) Mechanistic diversity in ATP-binding cassette(ABC) transporters. Nat Struct Mol Biol 23:487-493
    Martin GM et al (2017a) Anti-diabetic drug binding site in a mammalian KATP channel revealed by Cryo-EM. Elife. https://doi.org/10.7554/eLife.31054
    Martin GM et al (2017b) Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating. Elife. https://doi.org/10.7554/eLife.24149
    Matsuo M et al (1999a) ATP binding properties of the nucleotidebinding folds of SUR1. J Biol Chem 274:37479-37482
    Matsuo M et al (1999b) NEM modification prevents high-affinity ATP binding to the first nucleotide binding fold of the sulphonylurea receptor, SUR1. FEBS Lett 458:292-294
    Nichols CG et al (1996) Adenosine diphosphate as an intracellular regulator of insulin secretion. Science 272:1785-1787
    Ortiz D et al (2013) Reinterpreting the action of ATP analogs on K (ATP) channels. J Biol Chem 288:18894-18902
    Pettersen EF et al (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25:1605-1612
    Proks P et al (1999) Involvement of the N-terminus of Kir6.2 in the inhibition of the KATP channel by ATP. J Physiol 514(Pt 1):19-25
    Proks P et al (2010) Activation of the K(ATP) channel by Mgnucleotide interaction with SUR1. J Gen Physiol 136:389-405
    Punjani A et al (2017) cryoSPARC:algorithms for rapid unsupervised cryo-EM structure determination. Nat Methods 14:290-296
    Reimann F et al (1999) Involvement of the n-terminus of Kir6.2 in coupling to the sulphonylurea receptor. J Physiol 518(Pt 2):325-336
    Schwanstecher C et al (1994a) Interaction of tolbutamide and cytosolic nucleotides in controlling the ATP-sensitive K+ channel in mouse beta-cells. Br J Pharmacol 111:302-310
    Schwanstecher M et al (1994b) Identification of a 38-kDa high affinity sulfonylurea-binding peptide in insulin-secreting cells and cerebral cortex. J Biol Chem 269:17768-17771
    Shimomura K et al (2006) Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects. Diabetes 55:1705-1712
    Shyng S, Nichols CG (1997) Octameric stoichiometry of the KATP channel complex. J Gen Physiol 110:655-664
    Shyng SL, Nichols CG (1998) Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282:1138-1141
    Shyng S et al (1997) Regulation of KATP channel activity by diazoxide and MgADP. Distinct functions of the two nucleotide binding folds of the sulfonylurea receptor. J Gen Physiol 110:643-654
    Suloway C et al (2005) Automated molecular microscopy:the new Leginon system. J Struct Biol 151:41-60
    Ueda K et al (1997) MgADP antagonism to Mg2+-independent ATP binding of the sulfonylurea receptor SUR1. J Biol Chem 272:22983-22986
    Ueda K et al (1999) Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc Natl Acad Sci USA 96:1268-1272
    Vedovato N et al (2015) The nucleotide-binding sites of SUR1:a mechanistic model. Biophys J 109:2452-2460
    Vila-Carriles WH et al (2007) Defining a binding pocket for sulfonylureas in ATP-sensitive potassium channels. FASEB J 21:18-25
    Whorton MR, MacKinnon R (2011) Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium. Cell 147:199-208
    Whorton MR, MacKinnon R (2013) X-ray structure of the mammalian GIRK2-betagamma G-protein complex. Nature 498:190-197
    Woo SK et al (2013) The sulfonylurea receptor 1 (Sur1)-transient receptor potential melastatin 4 (Trpm4) channel. J Biol Chem 288:3655-3667
    Zhang K (2016) Gctf:real-time CTF determination and correction. J Struct Biol 193:1-12
    Zhang Z, Chen J (2016) Atomic structure of the cystic fibrosis transmembrane conductance regulator. Cell 167(1586-1597):e1589
    Zhang Z et al (2017) Conformational changes of CFTR upon phosphorylation and ATP binding. Cell 170(483-491):e488
    Zhao Y et al (2015) In vitro inhibition of AKR1Cs by sulphonylureas and the structural basis. Chem Biol Interact 240:310-315
    Zheng SQ et al (2017) MotionCor2:anisotropic correction of beaminduced motion for improved cryo-electron microscopy. Nat Methods 14:331-332
    Zhou M et al (2015) Atomic structure of the apoptosome:mechanism of cytochrome c-and dATP-mediated activation of Apaf-1. Genes Dev 29:2349-2361
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