J. A. Ballesteros and H. Weinstein, Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors, Methods Neurosci, vol.25, pp.366-428, 1995.

J. A. Baltos, K. J. Gregory, P. J. White, P. M. Sexton, A. Christopoulos et al., Quantification of adenosine A(1) receptor biased agonism: implications for drug discovery, Biochem. Pharmacol, vol.99, pp.101-112, 2016.

J. A. Baltos, S. Paoletta, A. T. Nguyen, K. J. Gregory, D. K. Tosh et al., Structure-activity analysis of biased agonism at the human Adenosine A3 receptor, Mol. Pharmacol, vol.90, pp.12-22, 2016.

H. Barbhaiya, R. Mcclain, A. Ijzerman, and S. A. Rivkees, Site-directed mutagenesis of the human A1 adenosine receptor: influences of acidic and hydroxy residues in the first four transmembrane domains on ligand binding, Mol. Pharmacol, vol.50, pp.1635-1642, 1996.

A. Batyuk, L. Galli, A. Ishchenko, G. W. Han, C. Gati et al., Native phasing of x-ray free-electron laser data for a G protein-coupled receptor, Sci. Adv, vol.2, p.1600292, 2016.

G. Burnstock, Purinergic signalling, Br. J. Pharmacol, vol.147, 2006.

M. Caffrey, A comprehensive review of the lipid cubic phase or in meso method for crystallizing membrane and soluble proteins and complexes, Acta Crystallogr. F Struct. Biol. Commun, vol.71, issue.1, pp.3-18, 2015.

B. Carpenter, T. , and C. G. , Engineering a minimal G protein to facilitate crystallisation of G protein-coupled receptors in their active conformation, Protein Eng. Des. Sel, vol.29, pp.583-594, 2016.

B. Carpenter, T. , and C. G. , Active state structures of G proteincoupled receptors highlight the similarities and differences in the G protein and arrestin coupling interfaces, Curr. Opin. Struct. Biol, vol.45, pp.124-132, 2017.

B. Carpenter, T. , and C. G. , Expression and purification of mini G proteins from Escherichia coli, Bio Protoc, vol.7, p.2235, 2017.

B. Carpenter, T. , and C. G. , Expression, purification and crystallisation of the Adenosine A 2A receptor bound to an engineered mini G protein, Bio Protoc, vol.7, p.2234, 2017.

B. Carpenter, R. Nehmé, T. Warne, A. G. Leslie, T. et al., Structure of the adenosine A 2A receptor bound to an engineered G protein, Nature, vol.536, pp.104-107, 2016.

J. F. Chen, H. K. Eltzschig, and B. B. Fredholm, Adenosine receptors as drug targets-what are the challenges?, Nat. Rev. Drug Discov, vol.12, pp.265-286, 2013.

R. K. Cheng, E. Segala, N. Robertson, F. Deflorian, A. S. Doré et al., Structures of human A 1 and A 2A adenosine receptors with xanthines reveal determinants of selectivity, Structure, vol.25, p.1274, 2017.

V. Cherezov, D. M. Rosenbaum, M. A. Hanson, S. G. Rasmussen, F. S. Thian et al., High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor, Science, vol.318, pp.1258-1265, 2007.

E. Chun, A. A. Thompson, W. Liu, C. B. Roth, M. T. Griffith et al., Fusion partner toolchest for the stabilization and crystallization of G protein-coupled receptors, Structure, vol.20, pp.967-976, 2012.

M. Cieslak, M. Komoszynski, and A. Wojtczak, Adenosine A(2A) receptors in Parkinson's disease treatment, Purinergic Signal, vol.4, pp.305-312, 2008.

M. Congreve, S. P. Andrews, A. S. Doré, K. Hollenstein, E. Hurrell et al., Discovery of 1,2,4-triazine derivatives as adenosine A 2A antagonists using structure based drug design, J. Med. Chem, vol.55, pp.1898-1903, 2012.

A. S. Doré, N. Robertson, J. C. Errey, I. Ng, K. Hollenstein et al., Structure of the adenosine A 2A receptor in complex with ZM241385 and the xanthines XAC and caffeine, Structure, vol.19, pp.1283-1293, 2011.

T. Flock, C. N. Ravarani, D. Sun, A. J. Venkatakrishnan, M. Kayikci et al., Universal allosteric mechanism for Galpha activation by GPCRs, Nature, vol.524, pp.173-179, 2015.

B. B. Fredholm, Adenosine-a physiological or pathophysiological agent?, J. Mol. Med, vol.92, pp.201-206, 2014.

B. B. Fredholm, A. P. Ijzerman, K. N. Klotz, and J. Linden, International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors, Pharmacol. Rev, vol.53, pp.527-552, 2001.

B. B. Fredholm, A. P. Ijzerman, K. A. Jacobson, J. Linden, and C. E. Müller, International union of basic and clinical pharmacology. LXXXI. nomenclature and classification of adenosine receptors-an update, Pharmacol. Rev, vol.63, pp.1-34, 2011.

Z. G. Gao, R. Balasubramanian, E. Kiselev, Q. Wei, and K. A. Jacobson, Probing biased/partial agonism at the G protein-coupled A 2B adenosine receptor, Biochem. Pharmacol, vol.90, pp.297-306, 2014.

P. R. Gentry, P. M. Sexton, C. , and A. , Novel allosteric modulators of G Protein-coupled receptors, J. Biol. Chem, vol.290, pp.19478-19488, 2015.

A. Glukhova, D. M. Thal, A. T. Nguyen, E. A. Vecchio, M. Jörg et al., Structure of the Adenosine A1 Receptor reveals the basis for subtype selectivity, Cell, vol.168, pp.867-877, 2017.

D. Guo, A. C. Pan, R. O. Dror, T. Mocking, R. Liu et al., Molecular basis of ligand dissociation from the Adenosine A 2A receptor, Mol. Pharmacol, vol.89, pp.485-491, 2016.

H. Gutiérrez-de-terán, A. Massink, D. Rodríguez, W. Liu, G. W. Han et al., The role of a sodium ion binding site in the allosteric modulation of the A 2A adenosine G protein-coupled receptor, Structure, vol.21, pp.2175-2185, 2013.

T. Hino, T. Arakawa, H. Iwanari, T. Yurugi-kobayashi, C. Ikeda-suno et al., G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody, Nature, vol.482, pp.237-240, 2012.

V. P. Jaakola, M. T. Griffith, M. A. Hanson, V. Cherezov, E. Y. Chien et al., The 2.6 angstrom crystal structure of a human A 2A adenosine receptor bound to an antagonist, Science, vol.322, pp.1211-1217, 2008.

K. A. Jacobson and Z. G. Gao, Adenosine receptors as therapeutic targets, Nat. Rev. Drug Discov, vol.5, pp.247-264, 2006.

A. Jazayeri, J. M. Dias, M. , and F. H. , From G protein-coupled receptor structure resolution to rational drug design, J. Biol. Chem, vol.290, pp.19489-19495, 2015.

V. Katritch, G. Fenalti, E. E. Abola, B. L. Roth, V. Cherezov et al., Allosteric sodium in class A GPCR signaling, Trends Biochem. Sci, vol.39, pp.233-244, 2014.

T. Kenakin, C. , and A. , Signalling bias in new drug discovery: detection, quantification and therapeutic impact, Nat. Rev. Drug Discov, vol.12, pp.205-216, 2013.

B. K. Kobilka and X. Deupi, Conformational complexity of G-protein-coupled receptors, Trends Pharmacol. Sci, vol.28, pp.397-406, 2007.

E. M. Landau and J. P. Rosenbusch, Lipidic cubic phases: a novel concept for the crystallization of membrane proteins, Proc. Natl. Acad. Sci. U.S.A, vol.93, pp.14532-14535, 1996.

G. Lebon, K. Bennett, A. Jazayeri, T. , and C. G. , Thermostabilisation of an agonist-bound conformation of the human adenosine A 2A receptor, J. Mol. Biol, vol.409, pp.298-310, 2011.

G. Lebon, P. C. Edwards, A. G. Leslie, T. , and C. G. , Molecular determinants of CGS21680 binding to the human Adenosine A 2A receptor, Mol. Pharmacol, vol.87, pp.907-915, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02067090

G. Lebon, T. Warne, T. , and C. G. , Agonist-bound structures of G protein-coupled receptors, Curr. Opin. Struct. Biol, vol.22, pp.482-490, 2012.

G. Lebon, T. Warne, P. C. Edwards, K. Bennett, C. J. Langmead et al., Agonist-bound adenosine A 2A receptor structures reveal common features of GPCR activation, Nature, vol.474, pp.521-525, 2011.

W. Liu, E. Chun, A. A. Thompson, P. Chubukov, F. Xu et al., Structural basis for allosteric regulation of GPCRs by sodium ions, Science, vol.337, pp.232-236, 2012.

F. Magnani, M. J. Serrano-vega, Y. Shibata, S. Abdul-hussein, G. Lebon et al., A mutagenesis and screening strategy to generate optimally thermostabilized membrane proteins for structural studies, Nat. Protoc, vol.11, pp.1554-1571, 2016.

F. Magnani, Y. Shibata, M. J. Serrano-vega, T. , and C. G. , Co-evolving stability and conformational homogeneity of the human adenosine A 2A receptor, Proc. Natl. Acad. Sci. U.S.A, vol.105, pp.10744-10749, 2008.

A. Manglik, T. H. Kim, M. Masureel, C. Altenbach, Z. Yang et al., Structural insights into the dynamic process of beta2-Adrenergic receptor signaling, Cell, vol.161, pp.1101-1111, 2015.

J. M. Martin-garcia, C. E. Conrad, G. Nelson, N. Stander, N. A. Zatsepin et al., Serial millisecond crystallography of membrane and soluble protein microcrystals using synchrotron radiation, IUCrJ, vol.4, pp.439-454, 2017.

I. Melnikov, V. Polovinkin, K. Kovalev, I. Gushchin, M. Shevtsov et al., Fast iodide-SAD phasing for highthroughput membrane protein structure determination, Sci. Adv, vol.3, p.1602952, 2017.

R. Moukhametzianov, M. Burghammer, P. C. Edwards, S. Petitdemange, D. Popov et al., Protein crystallography with a micrometre-sized synchrotron-radiation beam, Acta Crystallogr. D Biol. Crystallogr, vol.64, issue.2, pp.158-166, 2008.

C. E. Müller and K. A. Jacobson, Recent developments in adenosine receptor ligands and their potential as novel drugs, Biochim. Biophys. Acta, vol.1808, pp.1290-1308, 2011.

L. J. Murphree, M. A. Marshall, J. M. Rieger, T. L. Macdonald, and J. Linden, Human A 2A adenosine receptors: high-affinity agonist binding to receptor-G protein complexes containing Gbeta(4), Mol. Pharmacol, vol.61, pp.455-462, 2002.

R. Nehmé, B. Carpenter, A. Singhal, A. Strege, P. C. Edwards et al., Mini-G proteins: novel tools for studying GPCRs in their active conformation, PLoS ONE, vol.12, 2017.

R. S. Prosser, L. Ye, A. Pandey, and A. Orazietti, Activation processes in ligand-activated G protein-coupled receptors: a case study of the adenosine A 2A receptor, Bioessays, vol.39, p.1700072, 2017.

S. G. Rasmussen, H. J. Choi, J. J. Fung, E. Pardon, P. Casarosa et al., Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor, Nature, vol.469, pp.175-180, 2011.

S. G. Rasmussen, H. J. Choi, D. M. Rosenbaum, T. S. Kobilka, F. S. Thian et al., Crystal structure of the human beta2 adrenergic G-protein-coupled receptor, Nature, vol.450, pp.383-387, 2007.

S. G. Rasmussen, B. T. Devree, Y. Zou, A. C. Kruse, K. Y. Chung et al., Crystal structure of the beta2 adrenergic receptor-Gs protein complex, Nature, vol.477, pp.549-555, 2011.

D. M. Rosenbaum, V. Cherezov, M. A. Hanson, S. G. Rasmussen, F. S. Thian et al., GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function, Science, vol.318, pp.1266-1273, 2007.

D. M. Rosenbaum, S. G. Rasmussen, and B. K. Kobilka, The structure and function of G-protein-coupled receptors, Nature, vol.459, pp.356-363, 2009.

D. M. Rosenbaum, C. Zhang, J. A. Lyons, R. Holl, D. Aragao et al., Structure and function of an irreversible agonist-beta(2) adrenoceptor complex, Nature, vol.469, pp.236-240, 2011.

J. Sawynok, Adenosine receptor targets for pain, Neuroscience, vol.338, pp.1-18, 2016.

E. Segala, D. Guo, R. K. Cheng, A. Bortolato, F. Deflorian et al., Controlling the dissociation of ligands from the Adenosine A 2A receptor through modulation of salt bridge strength, J. Med. Chem, vol.59, pp.6470-6479, 2016.

M. J. Serrano-vega, F. Magnani, Y. Shibata, T. , and C. G. , Conformational thermostabilization of the beta1-adrenergic receptor in a detergent-resistant form, Proc. Natl. Acad. Sci. U.S.A, vol.105, pp.877-882, 2008.

Y. Shibata, J. F. White, M. J. Serrano-vega, F. Magnani, A. L. Aloia et al., Thermostabilization of the neurotensin receptor NTS1, J. Mol. Biol, vol.390, pp.262-277, 2009.

J. Steyaert and B. K. Kobilka, Nanobody stabilization of G proteincoupled receptor conformational states, Curr. Opin. Struct. Biol, vol.21, pp.567-572, 2011.

A. Strege, B. Carpenter, P. C. Edwards, T. , and C. G. , Strategy for the thermostabilization of an agonist-bound GPCR coupled to a G protein, Methods Enzymol, vol.594, pp.243-264, 2017.

B. Sun, P. Bachhawat, M. L. Chu, M. Wood, T. Ceska et al., Crystal structure of the adenosine A 2A receptor bound to an antagonist reveals a potential allosteric pocket, Proc. Natl. Acad. Sci. U.S.A, vol.114, pp.2066-2071, 2017.

C. G. Tate and G. F. Schertler, Engineering G protein-coupled receptors to facilitate their structure determination, Curr. Opin. Struct. Biol, vol.19, pp.386-395, 2009.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, F. M. Heydenreich, T. Flock et al., Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region, Nature, vol.536, pp.484-487, 2016.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler et al., Molecular signatures of G-protein-coupled receptors, Nature, vol.494, pp.185-194, 2013.

D. Verzijl and A. P. Ijzerman, Functional selectivity of adenosine receptor ligands, Purinergic Signal, vol.7, pp.171-192, 2011.

T. Warne, P. C. Edwards, A. G. Leslie, T. , and C. G. , Crystal structures of a stabilized beta1-adrenoceptor bound to the biased agonists bucindolol and carvedilol, Structure, vol.20, pp.841-849, 2012.

T. Warne, R. Moukhametzianov, J. G. Baker, R. Nehmé, P. C. Edwards et al., The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor, Nature, vol.469, pp.241-244, 2011.

T. Warne, M. J. Serrano-vega, J. G. Baker, R. Moukhametzianov, P. C. Edwards et al., Structure of a ? 1-adrenergic G-protein-coupled receptor, Nature, vol.454, pp.486-491, 2008.

T. Weinert, N. Olieric, R. Cheng, S. Brünle, D. James et al., Serial millisecond crystallography for routine roomtemperature structure determination at synchrotrons, Nat. Commun, vol.8, p.542, 2017.

G. H. Westfield, S. G. Rasmussen, M. Su, S. Dutta, B. T. Devree et al., Structural flexibility of the G alpha s alpha-helical domain in the ? 2-adrenoceptor Gs complex, Proc. Natl. Acad. Sci. U.S.A, vol.108, pp.16086-16091, 2011.

J. F. White, N. Noinaj, Y. Shibata, J. Love, B. Kloss et al., Structure of the agonist-bound neurotensin receptor, Nature, vol.490, pp.508-513, 2012.

F. Xu, H. Wu, V. Katritch, G. W. Han, K. A. Jacobson et al., Structure of an agonist-bound human A 2A adenosine receptor, Science, vol.332, pp.322-327, 2011.

L. Ye, N. Van-eps, M. Zimmer, O. P. Ernst, and R. S. Prosser, Activation of the A 2A adenosine G-protein-coupled receptor by conformational selection, Nature, vol.533, pp.265-268, 2016.