Structural Insights into IP3R Function

  • Irina I. Serysheva
  • Mariah R. Baker
  • Guizhen Fan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 981)


Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed intracellular ligand-gated Ca2+ channels present on the endoplasmic reticulum of virtually all eukaryotic cells. These channels mediate the Ca2+ release from intracellular stores in response to activation by the signaling molecule IP3, which functions to transmit diverse signals received by the cell, e.g. from hormones, neurotransmitters, growth factors and hypertrophic stimuli, to various signaling pathways within the cell. Thus, IP3R channels can be conceptualized as highly dynamic scaffold membrane protein complexes, where binding of ligands can change the scaffold structure leading to cellular Ca2+ signals that direct markedly different cellular actions. Although extensively characterized in physiological and biochemical studies, the detailed mechanisms of how IP3Rs produce highly controlled Ca2+ signals in response to diversified extra- and intracellular stimuli remains unknown and requires high-resolution knowledge of channel molecular architecture. Recently, single-particle electron cryomicroscopy (cryo-EM) has yielded a long-awaited near-atomic resolution structure of the entire full-length type 1 IP3R. This structure provides important insights into the molecular underpinnings of ligand-mediated activation and regulation of IP3R. In this chapter, we evaluate available information and research progress on the structure of IP3R channel in an attempt to shed light on its function.


Inositol 1,4,5-trisphosphate receptor Ca2+ release channel Near-atomic resolution structure Single-particle cryo-EM 



The authors thank Matthew L. Baker for his input on comparative analysis of Ca2+ release channels and for critiques on the manuscript. This work was supported by the National Institutes of Health (R01 GM072804), the American Heart Association (16GRNT29720001) and the Muscular Dystrophy Association (295138).


  1. 1.
    Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev 87:593–658CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bezprozvanny I (2007) Inositol 1,4,5-tripshosphate receptor, calcium signalling and Huntington’s disease. Subcell Biochem 45:323–335CrossRefPubMedGoogle Scholar
  3. 3.
    Jacobsen AN, Du XJ, Lambert KA, Dart AM, Woodcock EA (1996) Arrythmogenic action of thrombin during myocardial reperfusion via release of inositol 1,4,5-triphosphate. Circulation 93:23–26CrossRefPubMedGoogle Scholar
  4. 4.
    Marks AR (1997) Intracellular calcium-release channels: regulators of cell life and death. Am J Phys 272:H597–H605Google Scholar
  5. 5.
    Matsumoto M, Nakagawa T, Innoe T, Nagata E, Tanaka K, Takano H, Minowa O, Kuno J, Sakakibara S, Yamada M, Yoneshima H, Miyawaki A, Fukuuchi Y, Furuichi T, Okano H, Mikoshiba K, Noda T (1996) Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-triphosphate receptor. Nature 379:168–171CrossRefPubMedGoogle Scholar
  6. 6.
    Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, Tong KI, Yoshikawa F, Furuichi T, Iwai M, Michikawa T, Mikoshiba K, Ikura M (2002) Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature 420:696–700CrossRefPubMedGoogle Scholar
  7. 7.
    Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M (2005) Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor. Mol Cell 17:193–203CrossRefPubMedGoogle Scholar
  8. 8.
    Lin CC, Baek K, Lu Z (2011) Apo and InsP-bound crystal structures of the ligand-binding domain of an InsP receptor. Nat Struct Mol Biol 18:1172–1174CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Seo MD, Velamakanni S, Ishiyama N, Stathopulos PB, Rossi AM, Khan SA, Dale P, Li C, Ames JB, Ikura M, Taylor CW (2012) Structural and functional conservation of key domains in InsP3 and ryanodine receptors. Nature 483:108–112CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ludtke SJ, Tran TP, Ngo QT, Moiseenkova-Bell VY, Chiu W, Serysheva II (2011) Flexible architecture of IP3R1 by cryo-EM. Structure 19:1192–1199CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Murray SC, Flanagan J, Popova OB, Chiu W, Ludtke SJ, Serysheva II (2013) Validation of cryo-EM structure of IP(3)R1 channel. Structure 21:900–909CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Fan G, Baker ML, Wang Z, Baker MR, Sinyagovskiy PA, Chiu W, Ludtke SJ, Serysheva II (2015) Gating machinery of InsP3R channels revealed by electron cryomicroscopy. Nature 527:336–341CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Berridge MJ, Fain JN (1979) Inhibition of phosphatidylinositol synthesis and the inactivation of calcium entry after prolonged exposure of the blowfly salivary gland to 5-hydroxytryptamine. Biochem J 178:59–69CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Berridge MJ (1983) Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J 212:849–858CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature 306:67–69CrossRefPubMedGoogle Scholar
  16. 16.
    Ehrlich BE, Watras J (1988) Inositol 1,4,5-trisphosphate activates a channel from smooth muscle sarcoplasmic reticulum. Nature 336:583–586CrossRefPubMedGoogle Scholar
  17. 17.
    Ferris CD, Huganir RL, Supattapone S, Snyder SH (1989) Purified inositol 1,4,5-trisphosphate receptor mediates calcium flux in reconstituted lipid vesicles. Nature 342:87–89CrossRefPubMedGoogle Scholar
  18. 18.
    Iino M (1987) Calcium dependent inositol trisphosphate-induced calcium release in the guinea-pig taenia caeci. Biochem Biophys Res Commun 142:47–52CrossRefPubMedGoogle Scholar
  19. 19.
    Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K (1989) Primary structure and functional expression of the inositol 1,4,5- trisphosphate-binding protein P400. Nature 342:32–38CrossRefPubMedGoogle Scholar
  20. 20.
    Mignery GA, Sudhof TC, Takei K, De Camilli P (1989) Putative receptor for inositol 1,4,5-trisphosphate similar to ryanodine receptor. Nature 342:192–195CrossRefPubMedGoogle Scholar
  21. 21.
    Mignery GA, Newton CL, Archer BT, Sudhof TC (1990) Structure and expression of the rat inositol 1,4,5-trisphosphate receptor. J Biol Chem 265:12679–12685PubMedGoogle Scholar
  22. 22.
    Yoshikawa S, Tanimura T, Miyawaki A, Nakamura M, Yuzaki M, Furuichi T, Mikoshiba K (1992) Molecular cloning and characterization of the inositol 1,4,5-trisphosphate receptor in Drosophila melanogaster. J Biol Chem 267:16613–16619PubMedGoogle Scholar
  23. 23.
    Takei K, Mignery GA, Mugnaini E, Sudhof TC, De Camilli P (1994) Inositol 1,4,5-trisphosphate receptor causes formation of ER cisternal stacks in transfected fibroblasts and in cerebellar Purkinje cells. Neuron 12:327–342CrossRefPubMedGoogle Scholar
  24. 24.
    Katayama E, Funahashi H, Michikawa T, Shiraishi T, Ikemoto T, Lino M, Hirosawa K, Mikoshiba K (1996) Native structure and arrangement of inositol-1,4,5-triphosphate receptor molecules in bovine cerebellar Purkinje cells as studied by quick-freeze deep-etch electron microscopy. EMBO J 15:4844–4851PubMedPubMedCentralGoogle Scholar
  25. 25.
    Chadwick CC, Saito A, Fleischer S (1990) Isolation and characteriztion of the inositol triphosphate receptor from smooth muscle. Proc Natl Acad Sci 87:2132–2136CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Jiang QX, Thrower EC, Chester DW, Ehrlich BE, Sigworth FJ (2002) Three-dimensional structure of the type 1 inositol 1,4,5-trisphosphate receptor at 24 A resolution. EMBO J 21:3575–3581CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Hamada K, Miyata T, Mayanagi K, Hirota J, Mikoshiba K (2002) Two-state conformational changes in inositol 1,4,5-trisphosphate receptor regulated by calcium. J Biol Chem 277:21115–21118CrossRefPubMedGoogle Scholar
  28. 28.
    Da Fonseca PC, Morris SA, Nerou EP, Taylor CW, Morris EP (2003) Domain organization of the type 1 inositol 1,4,5-trisphosphate receptor as revealed by single-particle analysis. Proc Natl Acad Sci U S A 100:3936–3941CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Serysheva II, Bare DJ, Ludtke SJ, Kettlun CS, Chiu W, Mignery GA (2003) Structure of the type 1 inositol 1,4,5-trisphosphate receptor revealed by electron cryomicroscopy. J Biol Chem 278:21319–21322CrossRefPubMedGoogle Scholar
  30. 30.
    Hamada K, Terauchi A, Mikoshiba K (2003) Three-dimensional rearrangements within inositol 1, 4, 5-trisphosphate receptor by calcium. J Biol Chem 278:52881–52889CrossRefPubMedGoogle Scholar
  31. 31.
    Sato C, Hamada K, Ogura T, Miyazawa A, Iwasaki K, Hiroaki Y, Tani K, Terauchi A, Fujiyoshi Y, Mikoshiba K (2004) Inositol 1,4,5-trisphosphate receptor contains multiple cavities and L-shaped ligand-binding domains. J Mol Biol 336:155–164CrossRefPubMedGoogle Scholar
  32. 32.
    Chan J, Whitten AE, Jeffries CM, Bosanac I, Mal TK, Ito J, Porumb H, Michikawa T, Mikoshiba K, Trewhella J, Ikura M (2007) Ligand-induced conformational changes via flexible linkers in the amino-terminal region of the inositol 1,4,5-trisphosphate receptor. J Mol Biol 373:1269–1280CrossRefPubMedGoogle Scholar
  33. 33.
    Hamada K, Miyatake H, Terauchi A, Mikoshiba K (2017) IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography. Proc Natl Acad Sci USA 114:4661–4666CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Maeda N, Niinobe M, Nakahira K, Mikoshiba K (1988) Purification and characterization of P400 protein, a glycoprotein characteristic of Purkinje cell, from mouse cerebellum. J Neurochem 51:1724–1730CrossRefPubMedGoogle Scholar
  35. 35.
    Supattapone S, Worley PF, Baraban JM, Snyder SH (1988) Solubilization, purification and characteriztion of an inositol triphosphate receptor. J Biol Chem 263:1530–1534PubMedGoogle Scholar
  36. 36.
    Maeda N, Niinobe M, Mikoshiba K (1990) A cerebellar Purkinje cell marker P400 protein is an inositol 1,4,5-triphosphate (insP3) receptor protein. Purification and characterization of InsP3 receptor complex. EMBO J 9:61–67PubMedPubMedCentralGoogle Scholar
  37. 37.
    Li C, Enomoto M, Rossi AM, Seo MD, Rahman T, Stathopulos PB, Taylor CW, Ikura M, Ames JB (2013) CaBP1, a neuronal Ca2+ sensor protein, inhibits inositol trisphosphate receptors by clamping intersubunit interactions. Proc Natl Acad Sci U S A 110:8507–8512CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Taylor CW, Tovey SC (2010) IP(3) receptors: toward understanding their activation. Cold Spring Harb Perspect Biol 2:a004010CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Tung CC, Lobo PA, Kimlicka L, Van Petegem F (2010) The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule. Nature 468:585–588CrossRefPubMedGoogle Scholar
  40. 40.
    Yuchi Z, Lau K, Van Petegem F (2012) Disease mutations in the ryanodine receptor central region: crystal structures of a phosphorylation hot spot domain. Structure 20:1201–1211CrossRefPubMedGoogle Scholar
  41. 41.
    Baker MR, Fan G, Serysheva II (2015) Single-particle cryo-EM of the ryanodine receptor channel in an aqueous environment. Eur J Transl Myol 25:4803CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Ludtke SJ, Serysheva II (2013) Single-particle cryo-EM of calcium release channels: structural validation. Curr Opin Struct Biol 23:755–762CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Stewart A, Grigorieff N (2004) Noise bias in the refinement of structures derived from single particles. Ultramicroscopy 102:67–84CrossRefPubMedGoogle Scholar
  44. 44.
    Serysheva II, Ludtke SJ (2010) 3D Structure of IP(3) Receptor. Curr Top Membr 66C:171–189CrossRefGoogle Scholar
  45. 45.
    Henderson R, Chen S, Chen JZ, Grigorieff N, Passmore LA, Ciccarelli L, Rubinstein JL, Crowther RA, Stewart PL, Rosenthal PB (2011) Tilt-pair analysis of images from a range of different specimens in single-particle electron cryomicroscopy. J Mol Biol 413:1028–1046CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Rosenthal PB, Henderson R (2003) Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J Mol Biol 333:721–745CrossRefPubMedGoogle Scholar
  47. 47.
    Scheres SH, Chen S (2012) Prevention of overfitting in cryo-EM structure determination. Nat Methods 9:853–854CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Gao Y, Cao E, Julius D, Cheng Y (2016) TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature 534:347–351CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Hite RK, Yuan P, Li Z, Hsuing Y, Walz T, Mackinnon R (2015) Cryo-electron microscopy structure of the Slo2.2 Na(+)-activated K(+) channel. Nature 527:198–203CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:107–112CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Matthies D, Dalmas O, Borgnia MJ, Dominik PK, Merk A, Rao P, Reddy BG, Islam S, Bartesaghi A, Perozo E, Subramaniam S (2016) Cryo-EM structures of the magnesium channel corA reveal symmetry break upon gating. Cell 164:747–756CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D (2015) Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 520:511–517CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Shen PS, Yang X, Decaen PG, Liu X, Bulkley D, Clapham DE, Cao E (2016) The structure of the polycystic kidney disease channel PKD2 in lipid nanodiscs. Cell 167:763–773. e11CrossRefPubMedGoogle Scholar
  54. 54.
    Wang W, Mackinnon R (2017) Cryo-EM structure of the open human ether-a-go-go-related K+ channel hERG. Cell 169:422–430. e10CrossRefPubMedGoogle Scholar
  55. 55.
    Whicher JR, Mackinnon R (2016) Structure of the voltage-gated K(+) channel Eag1 reveals an alternative voltage sensing mechanism. Science 353:664–669CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Wu J, Yan Z, Li Z, Qian X, Lu S, Dong M, Zhou Q, Yan N (2016) Structure of the voltage-gated calcium channel Cav1.1 at 3.6 A resolution. Nature 537:191–196CrossRefPubMedGoogle Scholar
  57. 57.
    Zubcevic L, Herzik MA Jr, Chung BC, Liu Z, Lander GC, Lee SY (2016) Cryo-electron microscopy structure of the TRPV2 ion channel. Nat Struct Mol Biol 23:180–186CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Bai XC, Yan Z, Wu J, Li Z, Yan N (2016) The central domain of RyR1 is the transducer for long-range allosteric gating of channel opening. Cell Res 26:995–1006CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Des Georges A, Clarke OB, Zalk R, Yuan Q, Condon KJ, Grassucci RA, Hendrickson WA, Marks AR, Frank J (2016) Structural basis for gating and activation of RyR1. Cell 167:145–157. e17CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Efremov RG, Leitner A, Aebersold R, Raunser S (2015) Architecture and conformational switch mechanism of the ryanodine receptor. Nature 517:39–43CrossRefPubMedGoogle Scholar
  61. 61.
    Wei R, Wang X, Zhang Y, Mukherjee S, Zhang L, Chen Q, Huang X, Jing S, Liu C, Li S, Wang G, Xu Y, Zhu S, Williams AJ, Sun F, Yin CC (2016) Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1. Cell Res 26:977–994CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Yan Z, Bai XC, Yan C, Wu J, Li Z, Xie T, Peng W, Yin CC, Li X, Scheres SH, Shi Y, Yan N (2015) Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. Nature 517:50–55CrossRefPubMedGoogle Scholar
  63. 63.
    Zalk R, Clarke OB, Des Georges A, Grassucci RA, Reiken S, Mancia F, Hendrickson WA, Frank J, Marks AR (2015) Structure of a mammalian ryanodine receptor. Nature 517:44–49CrossRefPubMedGoogle Scholar
  64. 64.
    Bai XC, Yan C, Yang G, Lu P, Ma D, Sun L, Zhou R, Scheres SH, Shi Y (2015) An atomic structure of human gamma-secretase. Nature 525:212–217CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Bartesaghi A, Merk A, Banerjee S, Matthies D, Wu X, Milne JLS, Subramaniam S (2015) 2.2 Å resolution cryo-EM structure of β-galactosidase in complex with a cell-permeant inhibitor. Science 348:1147–1151CrossRefPubMedGoogle Scholar
  66. 66.
    Jiang J, Pentelute BL, Collier RJ, Zhou ZH (2015) Atomic structure of anthrax protective antigen pore elucidates toxin translocation. Nature 521:545–549CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Merk A, Bartesaghi A, Banerjee S, Falconieri V, Rao P, Davis MI, Pragani R, Boxer MB, Earl LA, Milne JL, Subramaniam S (2016) Breaking cryo-EM resolution barriers to facilitate drug discovery. Cell 165:1698–1707CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Kuhlbrandt W (2014) Cryo-EM enters a new era. elife 3:e03678CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Liao M, Cao E, Julius D, Cheng Y (2014) Single particle electron cryo-microscopy of a mammalian ion channel. Curr Opin Struct Biol 27:1–7CrossRefPubMedGoogle Scholar
  70. 70.
    Milne JL, Borgnia MJ, Bartesaghi A, Tran EE, Earl LA, Schauder DM, Lengyel J, Pierson J, Patwardhan A, Subramaniam S (2013) Cryo-electron microscopy—a primer for the non-microscopist. FEBS J 280:28–45CrossRefPubMedGoogle Scholar
  71. 71.
    Subramaniam S, Earl LA, Falconieri V, Milne JL, Egelman EH (2016) Resolution advances in cryo-EM enable application to drug discovery. Curr Opin Struct Biol 41:194–202CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Kucukelbir A, Sigworth FJ, Tagare HD (2014) Quantifying the local resolution of cryo-EM density maps. Nat Methods 11:63–65CrossRefPubMedGoogle Scholar
  73. 73.
    Chen S, Mcmullan G, Faruqi AR, Murshudov GN, Short JM, Scheres SH, Henderson R (2013) High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135:24–35CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Baker MR, Fan G, Serysheva II (2017) Structure of IP3R channel: high-resolution insights from cryo-EM. Curr Opin Struct Biol 46:38–47CrossRefPubMedGoogle Scholar
  75. 75.
    Yoshikawa F, Morita M, Monkawa T, Michikawa T, Furuichi T, Mikoshiba K (1996) Mutational analysis of the ligand binding site of the inositol 1,4,5- trisphosphate receptor. J Biol Chem 271:18277–18284CrossRefPubMedGoogle Scholar
  76. 76.
    Yoshikawa F, Iwasaki H, Michikawa T, Furuichi T, Mikoshiba K (1999) Trypsinized cerebellar inositol 1,4,5-trisphosphate receptor. Structural and functional coupling of cleaved ligand binding and channel domains. J Biol Chem 274:316–327CrossRefPubMedGoogle Scholar
  77. 77.
    Yamazaki H, Chan J, Ikura M, Michikawa T, Mikoshiba K (2010) Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates functional coupling between ligand binding and channel opening. J Biol Chem 285:36081–36091CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Szlufcik K, Bultynck G, Callewaert G, Missiaen L, Parys JB, De Smedt H (2006) The suppressor domain of inositol 1,4,5-trisphosphate receptor plays an essential role in the protection against apoptosis. Cell Calcium 39:325–336CrossRefPubMedGoogle Scholar
  79. 79.
    Uchida K, Miyauchi H, Furuichi T, Michikawa T, Mikoshiba K (2003) Critical regions for activation gating of the inositol 1,4,5-trisphosphate receptor. J Biol Chem 278:16551–16560CrossRefPubMedGoogle Scholar
  80. 80.
    Schug ZT, Joseph SK (2006) The role of the S4-S5 linker and C-terminal tail in inositol 1,4,5-trisphosphate receptor function. J Biol Chem 281:24431–24440CrossRefPubMedGoogle Scholar
  81. 81.
    Ponting CP (2000) Novel repeats in ryanodine and IP3 receptors and protein O-mannosyltransferases. Trends Biochem Sci 25:48–50PubMedGoogle Scholar
  82. 82.
    Alzayady K, Sebe-Pedros A, Chandrasekhar R, Wang L, Ruiz-Trillo I, Yule DI (2015) Tracing the evolutionary history of Inositol, 1, 4, 5-Trisphosphate receptor: insights from analyses of capsaspora owczarzaki Ca2+ release channel orthologs. Mol Biol Evol 32(9):2236–2253CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Amador FJ, Liu S, Ishiyama N, Plevin MJ, Wilson A, Maclennan DH, Ikura M (2009) Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil domain reveals a disease-associated mutation “hot spot” loop. Proc Natl Acad Sci U S A 106:11040–11044CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Bezprozvanny I, Watras J, Ehrlich BE (1991) Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature 351:751–754CrossRefPubMedGoogle Scholar
  85. 85.
    Du GG, Maclennan DH (1998) Functional consequences of mutations of conserved, polar amino acids in transmembrane sequences of the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem 273:31867–31872CrossRefPubMedGoogle Scholar
  86. 86.
    Miyakawa T, Mizushima A, Hirose K, Yamazawa T, Bezprozvanny I, Kurosaki T, Iino M (2001) Ca2+-sensor region of IP(3) receptor controls intracellular Ca2+ signaling. EMBO J 20:1674–1680CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Serysheva II (2014) Toward a high-resolution structure of IP(3)R channel. Cell Calcium 56:125–132CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Popot JL, Althoff T, Bagnard D, Baneres JL, Bazzacco P, Billon-Denis E, Catoire LJ, Champeil P, Charvolin D, Cocco MJ, Cremel G, Dahmane T, De La Maza LM, Ebel C, Gabel F, Giusti F, Gohon Y, Goormaghtigh E, Guittet E, Kleinschmidt JH, Kuhlbrandt W, Le Bon C, Martinez KL, Picard M, Pucci B, Sachs JN, Tribet C, Van Heijenoort C, Wien F, Zito F, Zoonens M (2011) Amphipols from A to Z. Annu Rev Biophys 40:379–408CrossRefPubMedGoogle Scholar
  89. 89.
    Jensen KH, Brandt SS, Shigematsu H, Sigworth FJ (2016) Statistical modeling and removal of lipid membrane projections for cryo-EM structure determination of reconstituted membrane proteins. J Struct Biol 194:49–60CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Liu Y, Sigworth FJ (2014) Automatic cryo-EM particle selection for membrane proteins in spherical liposomes. J Struct Biol 185:295–302CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Wang L, Sigworth FJ (2009) Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy. Nature 461:292–295CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Irina I. Serysheva
    • 1
  • Mariah R. Baker
    • 1
  • Guizhen Fan
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, Structural Biology Imaging CenterMcGovern Medical School at The University of Texas Health Science CenterHoustonUSA

Personalised recommendations