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pp 1-26 | Cite as

NMR Spectroscopy for the Characterization of GPCR Energy Landscapes

  • Marina Casiraghi
  • Jean-Louis Banères
  • Laurent J. Catoire
Chapter
Part of the Topics in Medicinal Chemistry book series

Abstract

G protein-coupled receptor (GPCR)-mediated signal transduction has a central role in human physiology and implication in many diseases. Despite the tremendous number of X-ray crystallography structures published in the past decade, the molecular mechanisms of ligand-dependent signaling remain to be completed. In particular, very little information is available concerning the implication of receptor dynamics and conformational changes on GPCR ligand efficiency and coupling. In this context, mapping the conformational landscape of GPCRs, and how it is modulated by the membrane environment and allosteric and signaling partners, is fundamental in order to gain a clear picture of how the signaling mechanism proceeds. Solution-state nuclear magnetic resonance (NMR) is a powerful technique to study GPCR energy landscapes, i.e., conformational ensembles along activation and inactivation pathway, and associated kinetic barriers.

Keywords

Energy landscape Escherichia coli GPCR Perdeuteration Solution-state NMR 

Abbreviations

β-DDM

n-Dodecyl-beta-maltoside

BLT2

Leukotriene B4 human receptor 2

DEER

Double electron–electron resonance

GPCR

G protein-coupled receptor

LMNG

Lauryl maltose neopentyl glycol

MD

Molecular dynamics

MNG-3

Maltose neopentyl glycol-3

NB

Nano-bodies

NMR

Nuclear magnetic resonance

SDS

Sodium dodecyl sulfate

TET

Trifluoroethylthiol

TM

Transmembrane

References

  1. 1.
    Henzler-Wildman K, Kern D (2007) Dynamic personalities of proteins. Nature 450:964–972ADSPubMedCrossRefGoogle Scholar
  2. 2.
    Smock RG, Gierasch LM (2009) Sending signals dynamically. Science 324:198–203ADSPubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Staus DP, Strachan RT, Manglik A, Pani B, Kahsai AW, Kim TH, Wingler LM, Ahn S, Chatterjee A, Masoudi A, Kruse AC, Pardon E, Steyaert J, Weis WI, Prosser RS, Kobilka BK, Costa T, Lefkowitz RJ (2016) Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation. Nature 535:448–452ADSPubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Frauenfelder H, Sligar SG, Wolynes PG (1991) The energy landscapes and motions of proteins. Science 254:1598–1603ADSPubMedCrossRefGoogle Scholar
  5. 5.
    Lazaridis T, Karplus M (2003) Thermodynamics of protein folding: a microscopic view. Biophys Chem 100:367–395PubMedCrossRefGoogle Scholar
  6. 6.
    Katritch V, Cherezov V, Stevens RC (2012) Diversity and modularity of G protein-coupled receptor structures. Trends Pharmacol Sci 33:17–27PubMedCrossRefGoogle Scholar
  7. 7.
    Choe H-W, Park JH, Kim YJ, Ernst OP (2011) Transmembrane signaling by GPCRs: insight from rhodopsin and opsin structures. Neuropharmacology 60:52–57PubMedCrossRefGoogle Scholar
  8. 8.
    Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, Kato HE, Livingston KE, Thorsen TS, Kling RC, Granier S, Gmeiner P, Husbands SM, Traynor JR, Weis WI, Steyaer J, Dror RO, Kobilka BK (2015) Structural insights into μ-opioid receptor activation. Nature 524:315–321ADSPubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Katritch V, Cherezov V, Stevens RC (2013) Structure-function of the G-protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 53:531–556PubMedCrossRefGoogle Scholar
  10. 10.
    Kruse AC (2015) Structural insights into activation and allosteric modulation of G protein-coupled receptors. Multifaceted roles of crystallography in modern drug discovery. Springer, Dordrecht, pp 19–26Google Scholar
  11. 11.
    Lee Y, Choi S, Hyeon C (2015) Communication over the network of binary switches regulates the activation of A2A adenosine receptor. PLoS Comput Biol 11:e1004044ADSPubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Xu F, Wu H, Katritch V, Han GW, Jacobson KA, Gao Z-G, Cherezov V, Stevens RC (2011) Structure of an agonist-bound human A2A adenosine receptor. Science 332:322–327ADSPubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Takuya K, Stevens RC, Iwata S (2011) Structure of the human histamine H1 receptor complex with doxepin. Nature 475:65–70PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola V-P, Chien EYT, Velasquez J, Kuhn P, Stevens RC (2008) A specific cholesterol binding site is established by the 2.8 Å structure of the human β2-adrenergic receptor. Structure 16:897–905PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Katritch V, Fenalti G, Abola EE, Roth BL, Cherezov V, Stevens RC (2014) Allosteric sodium in class A GPCR signaling. Trends Biochem Sci 39:233–244PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Liu JJ, Horst R, Katritch V, Stevens RC, Wuthrich K (2012) Biased signaling pathways in 2-adrenergic receptor characterized by 19F-NMR. Science 335:1106–1110ADSPubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Fenalti G, Giguere PM, Katritch V, Huang X-P, Thompson AA, Cherezov V, Roth BL, Stevens RC (2014) Molecular control of δ-opioid receptor signalling. Nature 506:191–196ADSPubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Granier S, Kobilka B (2012) A new era of GPCR structural and chemical biology. Nat Chem Biol 8:670–673PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Chung KY, Rasmussen SGF, Liu T, Li S, DeVree BT, Chae PS, Calinski D, Kobilka BK, Woods VL, Sunahara RK (2011) Conformational changes in the G protein Gs induced by the β2 adrenergic receptor. Nature 477:611–615ADSPubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MHE, Zhang C, Moeller A, West GM, Pascal B, Van Eps N, Caro LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi X, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad C, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Howe N, Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JCH, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE (2015) Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523:561–567ADSPubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Manglik A, Kim TH, Masureel M, Altenbach C, Yang Z, Hilger D, Lerch MT, Kobilka TS, Thian FS, Hubbell WL, Prosser RS, Kobilka BK (2015) Structural insights into the dynamic process of β2-adrenergic receptor signaling. Cell 161:1101–1111PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    De Zorzi R, Mi W, Liao M, Walz T (2016) Single-particle electron microscopy in the study of membrane protein structure. Microscopy 65:81–96PubMedCrossRefGoogle Scholar
  23. 23.
    Gregorio GG, Masureel M, Hilger D, Terry DS, Juette M, Zhao H, Zhou Z, Perez-Aguilar JM, Hauge M, Mathiasen S, Javitch JA, Weinstein H, Kobilka BK, Blanchard SC (2017) Single-molecule analysis of ligand efficacy in β2AR–G-protein activation. Nature 547(7661):68–73.  https://doi.org/10.1038/nature22354 ADSPubMedCrossRefGoogle Scholar
  24. 24.
    Tian H, Fürstenberg A, Huber T (2017) Labeling and single-molecule methods to monitor G protein-coupled receptor dynamics. Chem Rev 117:186–245PubMedCrossRefGoogle Scholar
  25. 25.
    Dror RO, Dirks RM, Grossman JP, Xu H, Shaw DE (2012) Biomolecular simulation: a computational microscope for molecular biology. Annu Rev Biophys 41:429–452PubMedCrossRefGoogle Scholar
  26. 26.
    Zocher M, Zhang C, Rasmussen SGF, Kobilka BK, Muller DJ (2012) Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor. Proc Natl Acad Sci U S A 109:3463–3472ADSCrossRefGoogle Scholar
  27. 27.
    Damian M, Mary S, Maingot M, M’Kadmi C, Gagne D, Leyris J-P, Denoyelle S, Gaibelet G, Gavara L, Garcia de Souza Costa M, Perahia D, Trinquet E, Mouillac B, Galandrin S, Galès S, Fehrentz J-A, Floquet N, Martinez J, Marie J, Banères J-L (2015) Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor: Gq complex. Proc Natl Acad Sci U S A 112:1601–1606ADSPubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    M’Kadmi C, Leyris J-P, Onfroy L, Galés C, Saulière A, Gagne D, Damian M, Mary S, Maingot M, Denoyelle S, Verdié P, Fehrentz J-A, Martinez J, Banères JL, Marie J (2015) Agonism, antagonism, and inverse agonism bias at the ghrelin receptor signaling. J Biol Chem 290:27021–27039PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Mary S, Damian M, Louet M, Floquet N, Fehrentz J-A, Marie J, Martinez J, Banères J-L (2012) Ligands and signaling proteins govern the conformational landscape explored by a G protein-coupled receptor. Proc Natl Acad Sci U S A 109:8304–8309ADSPubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Vogel R, Mahalingam M, Lüdeke S, Huber T, Siebert F, Sakmar TP (2008) Functional role of the “ionic lock”-an interhelical hydrogen-bond network in family A heptahelical receptors. J Mol Biol 380:648–655PubMedCrossRefGoogle Scholar
  31. 31.
    Kay LE (2016) New views of functionally dynamic proteins by solution NMR spectroscopy. J Mol Biol 428:323–331PubMedCrossRefGoogle Scholar
  32. 32.
    Mertz B, Struts AV, Feller SE, Brown MF (2012) Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation. Biochim Biophys Acta 1818:241–251PubMedCrossRefGoogle Scholar
  33. 33.
    Park SH, Das BB, Casagrande F, Tian Y, Nothnagel HJ, Chu M, Kiefer H, Maier K, De Angelis AA, Marassi FM, Opella SJ (2012) Structure of the chemokine receptor CXCR1 in phospholipid bilayers. Nature 491:779–784ADSPubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kimura T, Vukoti K, Lynch DL, Hurst DP, Grossfield A, Pitman MC, Reggio PH, Yeliseev AA, Gawrisch K (2014) Global fold of human cannabinoid type 2 receptor probed by solid-state 13C-, 15N-MAS NMR and molecular dynamics simulations: NMR studies on CB2 receptor. Proteins: Struct Funct Bioinf 82:452–465CrossRefGoogle Scholar
  35. 35.
    Schrottke S, Kaiser A, Vortmeier G, Els-Heindl S, Worm D, Bosse M, Schmidt P, Scheidt HA, Beck-Sickinger AG, Huster D (2017) Expression, functional characterization, and solid-state NMR investigation of the G protein-coupled ghs receptor in bilayer membranes. Sci Rep 7:46128ADSPubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Goto NK, Gardner KH, Mueller GA, Willis RC, Kay LE (1999) A robust and cost-effective method for the production of Val, Leu, Ile (δ1) methyl-protonated 15N, 13C, 2H-labeled proteins. J Biomol NMR 13:369–374PubMedCrossRefGoogle Scholar
  37. 37.
    Kay LE (2011) Solution NMR spectroscopy of supra-molecular systems, why bother? A methyl-TROSY view. J Magn Reson 210:159–170ADSPubMedCrossRefGoogle Scholar
  38. 38.
    Rosenzweig R, Kay LE (2014) Bringing dynamic molecular machines into focus by methyl-TROSY NMR. Annu Rev Biochem 83:291–315PubMedCrossRefGoogle Scholar
  39. 39.
    Tugarinov V, Hwang PM, Kay LE (2004) Nuclear magnetic resonance spectroscopy of high-molecular-weight proteins. Annu Rev Biochem 73:107–146PubMedCrossRefGoogle Scholar
  40. 40.
    Tugarinov V, Kanelis V, Kay LE (2006) Isotope labeling strategies for the study of high-molecular-weight proteins by solution NMR spectroscopy. Nat Protoc 1:749–754PubMedCrossRefGoogle Scholar
  41. 41.
    Huang R, Ripstein ZA, Augustyniak R, Lazniewski M, Ginalski K, Kay LE, Rubinstein JL (2016) Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study. Proc Natl Acad Sci U S A 113:4190–4199CrossRefGoogle Scholar
  42. 42.
    Ruschak AM, Religa TL, Breuer S, Witt S, Kay LE (2010) The proteasome antechamber maintains substrates in an unfolded state. Nature 467:868–871ADSPubMedCrossRefGoogle Scholar
  43. 43.
    Sekhar A, Rosenzweig R, Bouvignies G, Kay LE (2016) Hsp70 biases the folding pathways of client proteins. Proc Natl Acad Sci U S A 113:2794–2801ADSCrossRefGoogle Scholar
  44. 44.
    Kenakin T (2002) Drug efficacy at G protein-coupled receptors. Annu Rev Pharmacol Toxicol 42:349–379PubMedCrossRefGoogle Scholar
  45. 45.
    Kleckner IR, Foster MP (2011) An introduction to NMR-based approaches for measuring protein dynamics. Biochim Biophys Acta 1814:942–968PubMedCrossRefGoogle Scholar
  46. 46.
    Baldwin AJ, Kay LE (2009) NMR spectroscopy brings invisible protein states into focus. Nat Chem Biol 5:808–814PubMedCrossRefGoogle Scholar
  47. 47.
    Sekhar A, Kay LE (2013) NMR paves the way for atomic level descriptions of sparsely populated, transiently formed biomolecular conformers. Proc Natl Acad Sci U S A 110:12867–12874ADSPubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Sekhar A, Vallurupalli P, Kay LE (2013) Defining a length scale for millisecond-timescale protein conformational exchange. Proc Natl Acad Sci U S A 110:11391–11396ADSPubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Shen Y, Lange O, Delaglio F, Rossi P, Aramini JM, Liu G, Eletsky A, Wu Y, Singarapu KK, Lemak A, Ignatchenko A, Arrowsmith CH, Szyperski T, Montelione GT, Baker D, Bax A (2008) Consistent blind protein structure generation from NMR chemical shift data. Proc Natl Acad Sci U S A 105:4685–4690ADSPubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Shen Y, Bax A (2015) Homology modeling of larger proteins guided by chemical shifts. Nat Methods 12:747–750PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Korzhnev DM, Religa TL, Banachewicz W, Fersht AR, Kay LE (2010) A transient and low-populated protein-folding intermediate at atomic resolution. Science 329:1312–1316ADSPubMedCrossRefGoogle Scholar
  52. 52.
    Bokoch MP, Zou Y, Rasmussen SGF, Liu CW, Nygaard R, Rosenbaum DM, Fung JJ, Choi H-J, Thian FS, Kobilka TS, Puglisi JD, Weis WI, Pardo L, Prosser RS, Mueller L, Kobilka BK (2010) Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. Nature 463:108–112ADSPubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Kim TH, Chung KY, Manglik A, Hansen AL, Dror RO, Mildorf TJ, Shaw DE, Kobilka BK, Prosser RS (2013) The role of ligands on the equilibria between functional states of a G protein-coupled receptor. J Am Chem Soc 135:9465–9474PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Kofuku Y, Ueda T, Okude J, Shiraishi Y, Kondo K, Maeda M, Tsujishita H, Shimada I (2012) Efficacy of the β2-adrenergic receptor is determined by conformational equilibrium in the transmembrane region. Nat Commun 3:1045ADSPubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Kofuku Y, Ueda T, Okude J, Shiraishi Y, Kondo K, Mizumura T, Suzuki S, Shimada I (2014) Functional dynamics of deuterated β2-adrenergic receptor in lipid bilayers revealed by NMR spectroscopy. Angew Chem Int Ed Engl 53:13376–13379PubMedCrossRefGoogle Scholar
  56. 56.
    Nygaard R, Zou Y, Dror RO, Mildorf TJ, Arlow DH, Manglik A, Pan AC, Liu CW, Fung JJ, Bokoch MP, Thian FS, Kobilka TS, Shaw DE, Mueller L, Prosser RS, Kobilka BK (2013) The dynamic process of β(2)-adrenergic receptor activation. Cell 152:532–542PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Okude J, Ueda T, Kofuku Y, Sato M, Nobuyama N, Kondo K, Shiraishi Y, Mizumura T, Onishi K, Natsume M, Maeda M, Tsujishita H, Kuranaga T, Inoue M, Shimada I (2015) Identification of a conformational equilibrium that determines the efficacy and functional selectivity of the μ-opioid receptor. Angew Chem Int Ed 54:15771–15776CrossRefGoogle Scholar
  58. 58.
    Sounier R, Mas C, Steyaert J, Laeremans T, Manglik A, Huang W, Kobilka BK, Déméné H, Granier S (2015) Propagation of conformational changes during μ-opioid receptor activation. Nature 524:375–378ADSPubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Ye L, Van Eps N, Zimmer M, Ernst OP, Prosser RS (2016) Activation of the A2A adenosine G-protein-coupled receptor by conformational selection. Nature 533:265–268ADSPubMedCrossRefGoogle Scholar
  60. 60.
    Isogai S, Deupi X, Opitz C, Heydenreich FM, Tsai C-J, Brueckner F, Schertler GFX, Veprintsev DB, Grzesiek S (2016) Backbone NMR reveals allosteric signal transduction networks in the β1-adrenergic receptor. Nature 530:237–241ADSPubMedCrossRefGoogle Scholar
  61. 61.
    Tugarinov V, Hwang PM, Ollerenshaw JE, Kay LE (2003) Cross-correlated relaxation enhanced 1H[bond]13C NMR spectroscopy of methyl groups in very high molecular weight proteins and protein complexes. J Am Chem Soc 125:10420–10428PubMedCrossRefGoogle Scholar
  62. 62.
    Klein-Seetharaman J, Hwa J, Cai K, Altenbach C, Hubbell WL, Khorana HG (1999) Single-cysteine substitution mutants at amino acid positions 55–75, the sequence connecting the cytoplasmic ends of helices I and II in rhodopsin: reactivity of the sulfhydryl groups and their derivatives identifies a tertiary structure that changes upon light-activation. Biochemistry 38:7938–7944PubMedCrossRefGoogle Scholar
  63. 63.
    Chae PS, Rasmussen SGF, Rana RR, Gotfryd K, Chandra R, Goren MA, Kruse AC, Nurva S, Loland CJ, Pierre Y, Drew D, Popot JL, Picot D, Fox BG, Guan L, Gether U, Byrne B, Kobilka B, Gellman SH (2010) Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nat Methods 7:1003–1008PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Chung KY, Kim TH, Manglik A, Alvares R, Kobilka BK, Prosser RS (2012) Role of detergents in conformational exchange of a G protein-coupled receptor. J Biol Chem 287:36305–36311PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Casiraghi M, Damian M, Lescop E, Point E, Moncoq K, Morellet N, Levy D, Marie J, Guittet E, Banères J-L, Catoire JL (2016) Functional modulation of a G protein-coupled receptor conformational landscape in a lipid bilayer. J Am Chem Soc 138:11170–11175PubMedCrossRefGoogle Scholar
  66. 66.
    Liu D, Wüthrich K (2016) Ring current shifts in (19)F-NMR of membrane proteins. J Biomol NMR 65:1–5PubMedCrossRefGoogle Scholar
  67. 67.
    Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller JK, Spedding M, Mailman RB (2006) Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther 320:1–13PubMedCrossRefGoogle Scholar
  68. 68.
    Bayburt TH, Grinkova YV, Sligar SG (2002) Self-assembly of discoidal phospholipid bilayer nanoparticles with membrane scaffold proteins. Nano Lett 2:853–856ADSCrossRefGoogle Scholar
  69. 69.
    Ritchie TK, Grinkova YV, Bayburt TH, Denisov IG, Zolnerciks JK, Atkins WM, Sligar SG (2009) Reconstitution of membrane proteins in phospholipid bilayer nanodiscs. Methods Enzymol 464:211–231PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    O’Reilly DR, Miller L, Luckow VA (1994) Baculovirus expression vectors: a laboratory manual. Oxford University Press, New YorkGoogle Scholar
  71. 71.
    Lebon G, Warne T, Edwards PC, Bennett K, Langmead CJ, Leslie AGW, Tate CG (2011) Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 474:521–525PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Serrano-Vega MJ, Magnani F, Shibata Y, Tate CG (2008) Conformational thermostabilization of the β1-adrenergic receptor in a detergent-resistant form. Proc Natl Acad Sci U S A 105:877–882ADSPubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Warne T, Chirnside J, Schertler GFX (2003) Expression and purification of truncated, non-glycosylated turkey beta-adrenergic receptors for crystallization. Biochim Biophys Acta 1610:133–140Google Scholar
  74. 74.
    Popot J-L (2010) Amphipols, nanodiscs, and fluorinated surfactants: three nonconventional approaches to studying membrane proteins in aqueous solutions. Annu Rev Biochem 79:737–775PubMedCrossRefGoogle Scholar
  75. 75.
    Zhang Q, Tao H, Hong W-X (2011) New amphiphiles for membrane protein structural biology. Methods 55:318–323PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Carpenter B, Tate CG (2016) Engineering a minimal G protein to facilitate crystallisation of G protein-coupled receptors in their active conformation. Protein Eng Des Sel 29:583–594PubMedPubMedCentralGoogle Scholar
  77. 77.
    Carpenter B, Tate CG (2017) Active state structures of G protein-coupled receptors highlight the similarities and differences in the G protein and arrestin coupling interfaces. Curr Opin Struct Biol 45:124–132PubMedCrossRefGoogle Scholar
  78. 78.
    Magnani F, Serrano-Vega MJ, Shibata Y, Abdul-Hussein S, Lebon G, Miller-Gallacher J, Singhal A, Strege A, Thomas JA, Tate CG (2016) A mutagenesis and screening strategy to generate optimally thermostabilized membrane proteins for structural studies. Nat Protoc 11:1554–1571PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Tate CG, Lebon G (2015) Purification and crystallization of a thermostabilized agonist-bound conformation of the human adenosine A(2A) receptor. Methods Mol Biol 1335:17–27PubMedCrossRefGoogle Scholar
  80. 80.
    Janin J, Miller S, Chothia C (1988) Surface, subunit interfaces and interior of oligomeric proteins. J Mol Biol 204:155–164PubMedCrossRefGoogle Scholar
  81. 81.
    Tugarinov V, Kay LE (2005) Methyl groups as probes of structure and dynamics in NMR studies of high-molecular-weight proteins. Chembiochem 6:1567–1577PubMedCrossRefGoogle Scholar
  82. 82.
    Rosenzweig R, Kay LE (2016) Solution NMR spectroscopy provides an avenue for the study of functionally dynamic molecular machines: the example of protein disaggregation. J Am Chem Soc 138:1466–1477PubMedCrossRefGoogle Scholar
  83. 83.
    Kay LE (2005) NMR studies of protein structure and dynamics. J Magn Reson 173:193–207ADSPubMedCrossRefGoogle Scholar
  84. 84.
    Religa TL, Sprangers R, Kay LE (2010) Dynamic regulation of archaeal proteasome gate opening as studied by TROSY NMR. Science 328:98–102ADSPubMedCrossRefGoogle Scholar
  85. 85.
    Katz JJ, Crespi HL (1966) Deuterated organisms: cultivation and uses. Science 151(3715):1187–1194ADSPubMedCrossRefGoogle Scholar
  86. 86.
    Arcemisbehere L, Sen T, Boudier L, Balestre M-N, Gaibelet G, Detouillon E, Orcel H, Mendre C, Rahmeh R, Granier S, Vivès C, Fieschi F, Damian M, Durroux T, Banères JL, Mouillac B (2010) Leukotriene BLT2 receptor monomers activate the Gi2 GTP-binding protein more efficiently than dimers. J Biol Chem 285:6337–6347PubMedCrossRefGoogle Scholar
  87. 87.
    Banères J-L, Martin A, Hullot P, Girard J-P, Rossi J-C, Parello J (2003) Structure-based analysis of GPCR function: conformational adaptation of both agonist and receptor upon leukotriene B4 binding to recombinant BLT1. J Mol Biol 329:801–814PubMedCrossRefGoogle Scholar
  88. 88.
    Banères J-L, Popot J-L, Mouillac B (2011) New advances in production and functional folding of G-protein-coupled receptors. Trends Biotechnol 29:314–322PubMedCrossRefGoogle Scholar
  89. 89.
    Mouillac B, Banères J-L (2010) Mammalian membrane receptors expression as inclusion bodies in Escherichia coli. Methods Mol Biol 601:39–48PubMedCrossRefGoogle Scholar
  90. 90.
    Huang KS, Bayley H, Liao M-J, London E, Khorana HG (1981) Refolding of an integral membrane protein. Denaturation, renaturation, and reconstitution of intact bacteriorhodopsin and two proteolytic fragments. J Biol Chem 256:3802–3809PubMedGoogle Scholar
  91. 91.
    Lind C, Höjeberg B, Khorana HG (1981) Reconstitution of delipidated bacteriorhodopsin with endogenous polar lipids. J Biol Chem 256:8298–8305PubMedGoogle Scholar
  92. 92.
    London E, Khorana HG (1982) Denaturation and renaturation of bacteriorhodopsin in detergents and lipid-detergent mixtures. J Biol Chem 257:7003–7011PubMedGoogle Scholar
  93. 93.
    Pocanschi CL, Dahmane T, Gohon Y, Rappaport F, Apell H-J, Kleinschmidt JH, Popot J-L (2006) Amphipathic polymers: tools to fold integral membrane proteins to their active form. Biochemistry 45:13954–13961PubMedCrossRefGoogle Scholar
  94. 94.
    Popot J-L, Althoff T, Bagnard D, Banères J-L, Bazzacco P, Billon-Denis E, Catoire LJ, Champeil P, Charvolin D, Cocco MJ, Crémel G, Dahmane T, de la Maza LM, Ebel C, Gabel F, Giusti F, Gohon Y, Goormaghtigh E, Guittet E, Kleinschmidt JH, Kühlbrandt 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 40:379–408PubMedCrossRefGoogle Scholar
  95. 95.
    Popot J-L (2014) Folding membrane proteins in vitro: a table and some comments. Arch Biochem Biophys 564:314–326ADSPubMedCrossRefGoogle Scholar
  96. 96.
    Zoonens M, Popot J-L (2014) Amphipols for each season. J Membr Biol 247:759–796PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Dahmane T, Damian M, Mary S, Popot J-L, Banères J-L (2009) Amphipol-assisted in vitro folding of G protein-coupled receptors. Biochemistry 48:6516–6521PubMedCrossRefGoogle Scholar
  98. 98.
    Muller I, Sarramégna V, Renault M, Lafaquière V, Sebai S, Milon A, Talmont F (2008) The full-length μ-opioid receptor: a conformational study by circular dichroism in trifluoroethanol and membrane-mimetic environments. J Membr Biol 223:49–57PubMedCrossRefGoogle Scholar
  99. 99.
    Pucadyil TJ, Chattopadhyay A (2006) Role of cholesterol in the function and organization of G-protein coupled receptors. Prog Lipid Res 45:295–333PubMedCrossRefGoogle Scholar
  100. 100.
    Huber T, Botelho AV, Beyer K, Brown MF (2004) Membrane model for the G-protein-coupled receptor rhodopsin: hydrophobic interface and dynamical structure. Biophys J 86:2078–2100PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Chini B, Parenti M (2004) G-protein coupled receptors in lipid rafts and caveolae: how, when and why do they go there? J Mol Endocrinol 32:325–338PubMedCrossRefGoogle Scholar
  102. 102.
    Han DS, Wang SX, Weinstein H (2008) Active state-like conformational elements in the β2-AR and a photoactivated intermediate of rhodopsin identified by dynamic properties of GPCRs. Biochemistry 47:7317–7321PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Marina Casiraghi
    • 1
    • 2
    • 3
  • Jean-Louis Banères
    • 4
  • Laurent J. Catoire
    • 1
    • 2
    • 3
  1. 1.Laboratory of Physical and Chemical Biology of Membrane ProteinsInstitut de Biologie Physico-Chimique (IBPC), UMR 7099 CNRSParisFrance
  2. 2.Paris Diderot UniversityParisFrance
  3. 3.PSL Research UniversityParisFrance
  4. 4.Faculté de PharmacieInstitut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS – Université Montpellier – ENSCMMontpellierFrance

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