Dr. Xavier Deupi i Corral

Senior scientist
Condensed Matter Theory Group >>
Building/Room: WHGA/123

Paul Scherrer Institute
Forschungsstrasse 111
5232 Villigen PSI

G protein-coupled receptors (GPCRs) are a family of seven transmembrane helix proteins found in almost all eukaryotic organisms, with approximately 800 genes in the human genome. These membrane proteins are essential in cell physiology, as they can be activated by an extraordinary diversity of extracellular signals, such as photons, odorants, protonated amines, peptides or glycoprotein hormones. Activated receptors can then trigger cellular signaling cascades through interaction with intracellular heterotrimeric G proteins and arrestins. As malfunction of GPCRs is commonly translated into pathological outcomes, these proteins constitute one of the most attractive pharmaceutical targets, constituting the target of around 30% of currently marketed drugs.

Despite their physiological and therapeutical importance, our understanding of the ligand-induced molecular mechanisms of GPCR activation is hampered by the relative scarcity of structural data. In the last decade, advances in protein engineering, crystallization methods and X-ray crystallography techniques have allowed the determination of more than 150 crystal structures of 40 different GPCRs in complex with ligands of varied pharmacology, peptides and with other proteins.

In my research I aim to understand how extracellular ligands trigger the process of signal transduction in GPCRs. Using a combination of structural bioinformatics, molecular dynamics and data-mining of structure and sequence databases, I extract as much information as possible from experimentally determined protein structures. This knowledge is used to design new experiments and to build experimentally testable models of GPCR function that will lead to a better understanding of ligand selectivity and efficacy.

I am particularly interested in determine the molecular principles of ligand selectivity (i.e. how specific ligands recognize certain receptors), efficacy (i.e. how ligands activate GPCRs) and biased signaling (i.e. how specific ligands preferentially trigger certain signaling pathways).

People Position Telephone E-mail
Dr. Xavier Deupi Principal Investigator +41 56 310 3337 xavier.deupi@psi.ch
Dr. Pikyee Ma Postdoctoral researcher +41 56 310 5295 pik-yee.ma@psi.ch
Dr. Ramon Guixa Postdoctoral researcher +41 56 310 33 37 ramon.guixa@psi.ch
People Position Period
Dr. Eshita Mutt Postdoctoral researcher/ PSI-Fellow 2015 - 2019
Dr. Tilman Flock Postdoctoral researcher / ETH Fellow 2016-2018
Milos Matkovic PhD. Student 2013-2016
Dr. Chayne Piscitelli Postdoctoral researcher / ETH Fellow 2011-2016
Dr. Florian Brückner Postdoctoral researcher / Marie Curie and EMBO Fellow 2011-2014


  • An online resource for GPCR structure determination and analysis Munk C, Mutt E, Isberg V, Nikolajsen Louise F, Bibbe Janne M, Flock T, Hanson Michael A, Stevens Raymond C, Deupi X, Gloriam David E
    NATURE METHODS , (2019).
    DOI: 10.1038/s41592-018-0302-x(link is external)
  • Arrestin-1 engineering facilitates complex stabilization with native rhodopsin Haider Raphael S, Wilhelm F, Rizk A, Mutt E, Deupi X, Peterhans C, Mühle J, Berger P, Schertler Gebhard FX, Standfuss J, Ostermaier Martin K
    Scientific Reports 9, 439 (2019).
    DOI: 10.1038/s41598-018-36881-4(link is external)
  • Elucidating the Structure?Activity Relationship of the Pentaglutamic Acid Sequence of Minigastrin with Cholecystokinin Receptor Subtype 2 Ritler A, Shoshan Michal S, Deupi X, Wilhelm P, Schibli R, Wennemers H, Béhé M
    DOI: 10.1021/acs.bioconjchem.8b00849(link is external)


  • Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish Gerrard E, Mutt E, Nagata T, Koyanagi M, Flock T, Lesca E, Schertler Gebhard FX, Terakita A, Deupi X, Lucas Robert J
    Proceedings of the National Academy of Sciences 115, 6201 (2018).
    DOI: 10.1073/pnas.1721333115(link is external)
  • Crystal structure of rhodopsin in complex with a mini-G o sheds light on the principles of G protein selectivity Tsai C, Pamula F, Nehmé R, Mühle J, Weinert T, Flock T, Nogly P, Edwards Patricia C, Carpenter B, Gruhl T, Ma P, Deupi X, Standfuss J, Tate Christopher G, Schertler Gebhard FX
    Science Advances 4, eaat7052 (2018).
    DOI: 10.1126/sciadv.aat7052(link is external)
  • GPCR-SAS: A web application for statistical analyses on G protein-coupled receptors sequences Gomez Tamayo Jose Carlos, Olivella Mireia, Rios Santiago, Hoogstraat Marlous, Gonzalez Angel, Mayol Eduardo, Deupi Xavier, Campillo Mercedes, Cordomi Arnau
    PLOS ONE 13, e0199843 (2018).
    DOI: 10.1371/journal.pone.0199843(link is external)


  • The DRF motif of CXCR6 as chemokine receptor adaptation to adhesion Eugenin Eliseo A, Koenen A, Babendreyer A, Schumacher J, Pasqualon T, Schwarz N, Seifert A, Deupi X, Ludwig A, Dreymueller D
    PLOS ONE 12, e0173486 (2017).
    DOI: 10.1371/journal.pone.0173486(link is external)


  • Diverse activation pathways in class A GPCRs converge near the G protein-coupling region AJ Venkatakrishnan, X Deupi, G Lebon, FM Heydenreich, T Flock, T Miljus, S Balaji, M Bouvier, DB Veprintsev, CG Tate, GF Schertler and MM Babu
    Nature 536, 484-487 (2016).
    DOI: 10.1038/nature19107
  • Structural role of the T94I rhodopsin mutation in congenital stationary night blindness A Singhal, Y Guo, M Matkovic, G Schertler, X Deupi, EC Yan and J Standfuss
    EMBO Rep 17, 1431-1440 (2016).
    DOI: 10.15252/embr.201642671
  • Backbone NMR reveals allosteric signal transduction networks in the beta 1-adrenergic receptor S Isogai, X Deupi, C Opitz, FM Heydenreich, CJ Tsai, F Brueckner, GF Schertler, DB Veprintsev and S Grzesiek
    Nature 530, 237-241 (2016).
    DOI: 10.1038/nature16577
  • SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture M Hilbert, A Noga, D Frey, V Hamel, P Guichard, SH Kraatz, M Pfreundschuh, S Hosner, I Fluckiger, R Jaussi, MM Wieser, KM Thieltges, X Deupi, DJ Muller, RA Kammerer, P Gonczy, M Hirono and MO Steinmetz
    Nat Cell Biol 18, 393-403 (2016).
    DOI: 10.1038/ncb3329


  • Batch crystallization of rhodopsin for structural dynamics using an X-ray free-electron laser W Wu, P Nogly, J Rheinberger, LM Kick, C Gati, G Nelson, X Deupi, J Standfuss, G Schertler and V Panneels
    Acta Crystallogr F Struct Biol Commun 71, 856-860 (2015).
    DOI: 10.1107/S2053230X15009966
  • Probing G alpha i1 protein activation at single-amino acid resolution D Sun, T Flock, X Deupi, S Maeda, M Matkovic, S Mendieta, D Mayer, RJ Dawson, GF Schertler, MM Babu and DB Veprintsev
    Nat Struct Mol Biol 22, 686-694 (2015).
    DOI: 10.1038/nsmb.3070
  • A molecular pharmacologist's guide to G protein-coupled receptor crystallography CL Piscitelli, J Kean, C de Graaf and X Deupi
    Mol Pharmacol 88, 536-551 (2015).
    DOI: 10.1124/mol.115.099663
  • TMalphaDB and TMbetaDB: Web servers to study the structural role of sequence motifs in alpha-helix and beta-barrel domains of membrane proteins M Perea, I Lugtenburg, E Mayol, A Cordomi, X Deupi, L Pardo and M Olivella
    BMC Bioinformatics 16, 266 (2015).
    DOI: 10.1186/s12859-015-0699-5
  • Conformational activation of visual rhodopsin in native disc membranes E Malmerberg, MB-G PH, G Katona, X Deupi, D Arnlund, C Wickstrand, LC Johansson, S Westenhoff, E Nazarenko, GF Schertler, A Menzel, WJ de Grip and R Neutze
    Sci Signal 8, ra26 (2015).
    DOI: 10.1126/scisignal.2005646


  • Functional map of arrestin-1 at single amino acid resolution MK Ostermaier, C Peterhans, R Jaussi, X Deupi and J Standfuss
    Proc Natl Acad Sci U S A 111, 1825-1830 (2014).
    DOI: 10.1073/pnas.1319402111
  • Structural and functional characterization of alternative transmembrane domain conformations in VEGF receptor 2 activation S Manni, KS Mineev, D Usmanova, EN Lyukmanova, MA Shulepko, MP Kirpichnikov, J Winter, M Matkovic, X Deupi, AS Arseniev and K Ballmer-Hofer
    Structure 22, 1077-1089 (2014).
    DOI: 10.1016/j.str.2014.05.010
  • Coronin 1 regulates cognition and behavior through modulation of camp/protein kinase a signaling R Jayachandran, X Liu, S Bosedasgupta, P Muller, CL Zhang, D Moshous, V Studer, J Schneider, C Genoud, C Fossoud, F Gambino, M Khelfaoui, C Muller, D Bartholdi, H Rossez, M Stiess, X Houbaert, R Jaussi, D Frey, RA Kammerer, X Deupi, JP de Villartay, A Luthi, Y Humeau and J Pieters
    PLoS Biol 12, e1001820 (2014).
    DOI: 10.1371/journal.pbio.1001820
  • Retinal proteins - you can teach an old dog new tricks J Heberle, X Deupi and G Schertler
    Biochim Biophys Acta 1837, 531-532 (2014).
    DOI: 10.1016/j.bbabio.2014.02.019
  • Relevance of rhodopsin studies for GPCR activation X Deupi
    Biochim Biophys Acta 1837, 674-682 (2014).
    DOI: 10.1016/j.bbabio.2013.09.002
  • Molecular dynamics: a stitch in time X Deupi
    Nat Chem 6, 7-8 (2014).
    DOI: 10.1038/nchem.1832


  • Molecular signatures of G protein-coupled receptors AJ Venkatakrishnan, X Deupi, G Lebon, CG Tate, GF Schertler and MM Babu
    Nature 494, 185-194 (2013).
    DOI: 10.1038/nature11896
  • Insights into congenital stationary night blindness based on the structure of G90D rhodopsin A Singhal, MK Ostermaier, SA Vishnivetskiy, V Panneels, KT Homan, JJ Tesmer, D Veprintsev, X Deupi, VV Gurevich, GF Schertler and J Standfuss
    EMBO Rep 14, 520-526 (2013).
    DOI: 10.1038/embor.2013.44
  • Relation between sequence and structure in membrane proteins M Olivella, A Gonzalez, L Pardo and X Deupi
    Bioinformatics 29, 1589-1592 (2013).
    DOI: 10.1093/bioinformatics/btt249
  • Structure of beta-adrenergic receptors F Brueckner, CL Piscitelli, CJ Tsai, J Standfuss, X Deupi and GF Schertler
    Methods Enzymol 520, 117-151 (2013).
    DOI: 10.1016/B978-0-12-391861-1.00006-X


  • Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy R Rahmeh, M Damian, M Cottet, H Orcel, C Mendre, T Durroux, KS Sharma, G Durand, B Pucci, E Trinquet, JM Zwier, X Deupi, P Bron, JL Baneres, B Mouillac and S Granier
    Proc Natl Acad Sci U S A 109, 6733-6738 (2012).
    DOI: 10.1073/pnas.1201093109
  • Conserved activation pathways in G protein-coupled receptors X Deupi, J Standfuss and G Schertler
    Biochem Soc Trans 40, 383-388 (2012).
    DOI: 10.1042/BST20120001
  • Ligands stabilize specific GPCR conformations: But how? X Deupi, XD Li and GF Schertler
    Structure 20, 1289-1290 (2012).
    DOI: 10.1016/j.str.2012.07.009
  • Stabilized G protein binding site in the structure of constitutively active metarhodopsin-ii X Deupi, P Edwards, A Singhal, B Nickle, D Oprian, G Schertler and J Standfuss
    Proc Natl Acad Sci U S A 109, 119-124 (2012).
    DOI: 10.1073/pnas.1114089108
  • Quantification of structural distortions in the transmembrane helices of GPCRs X Deupi
    Humana Press Eds.: N Vaidehi and J Klein-Seetharaman) 219-235 (2012).
    DOI: 10.1007/978-1-62703-023-6_13


  • A structural insight into the reorientation of transmembrane domains 3 and 5 during family a G protein-coupled receptor activation K Sansuk, X Deupi, IR Torrecillas, A Jongejan, S Nijmeijer, RA Bakker, L Pardo and R Leurs
    Mol Pharmacol 79, 262-269 (2011).
    DOI: 10.1124/mol.110.066068
  • Molecular basis of ligand dissociation in beta-adrenergic receptors A Gonzalez, T Perez-Acle, L Pardo and X Deupi
    PLoS One 6, e23815 (2011).
    DOI: 10.1371/journal.pone.0023815
  • Structural insights into agonist-induced activation of G protein-coupled receptors X Deupi and J Standfuss
    Curr Opin Struct Biol 21, 541-551 (2011).
    DOI: 10.1016/j.sbi.2011.06.002


  • Tracking G protein-coupled receptor activation using genetically encoded infrared probes S Ye, E Zaitseva, G Caltabiano, GF Schertler, TP Sakmar, X Deupi and R Vogel
    Nature 464, 1386-1389 (2010).
    DOI: 10.1038/nature08948
  • Influence of the g- conformation of Ser and Thr on the structure of transmembrane helices X Deupi, M Olivella, A Sanz, N Dölker, M Campillo and L Pardo
    J Struct Biol 169, 116-123 (2010).
    DOI: 10.1016/j.jsb.2009.09.009
  • Energy landscapes as a tool to integrate GPCR structure, dynamics, and function X Deupi and BK Kobilka
    Physiology (Bethesda) 25, 293-303 (2010).
    DOI: 10.1152/physiol.00002.2010


  • The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex XJ Yao, G Velez Ruiz, MR Whorton, SG Rasmussen, BT DeVree, X Deupi, RK Sunahara and B Kobilka
    Proc Natl Acad Sci U S A 106, 9501-9506 (2009).
    DOI: 10.1073/pnas.0811437106
  • Ligand-regulated oligomerization of beta 2 adrenoceptors in a model lipid bilayer JJ Fung, X Deupi, L Pardo, XJ Yao, GA Velez-Ruiz, BT Devree, RK Sunahara and BK Kobilka
    EMBO J 28, 3315-3328 (2009).
    DOI: 10.1038/emboj.2009.267


  • Characterization of a conformationally sensitive TOAC spin-labeled substance P AM Shafer, CR Nakaie, X Deupi, VJ Bennett and JC Voss
    Peptides 29, 1919-1929 (2008).
    DOI: 10.1016/j.peptides.2008.08.002


  • The activation mechanism of chemokine receptor CCR5 involves common structural changes but a different network of interhelical interactions relative to rhodopsin JY Springael, C de Poorter, X Deupi, J Van Durme, L Pardo and M Parmentier
    Cell Signal 19, 1446-1456 (2007).
    DOI: 10.1016/j.cellsig.2007.01.022
  • The role of internal water molecules in the structure and function of the rhodopsin family of G protein-coupled receptors L Pardo, X Deupi, N Dolker, ML Lopez-Rodriguez and M Campillo
    Chembiochem 8, 19-24 (2007).
    DOI: 10.1002/cbic.200600429
  • Conformational complexity of G protein-coupled receptors BK Kobilka and X Deupi
    Trends Pharmacol Sci 28, 397-406 (2007).
    DOI: 10.1016/j.tips.2007.06.003
  • Charge-charge and cation-pi interactions in ligand binding to G protein-coupled receptors N Dölker, X Deupi, L Pardo and M Campillo
    Theoretical Chemistry Accounts 118, 579-588 (2007).
    DOI: 10.1007/s00214-007-0341-3
  • Activation of G protein-coupled receptors X Deupi and B Kobilka
    Adv Protein Chem 74, 137-166 (2007).
    DOI: 10.1016/S0065-3233(07)74004-4
  • Structural models of class a G protein-coupled receptors as a tool for drug design: insights on transmembrane bundle plasticity X Deupi, N Dölker, ML Lopez-Rodriguez, M Campillo, JA Ballesteros and L Pardo
    Curr Top Med Chem 7, 991-998 (2007).


  • Coupling ligand structure to specific conformational switches in the beta 2 adrenoceptor X Yao, C Parnot, X Deupi, VR Ratnala, G Swaminath, D Farrens and B Kobilka
    Nat Chem Biol 2, 417-422 (2006).
    DOI: 10.1038/nchembio801
  • 3D structure of G protein-coupled receptors L Pardo, X Deupi, C Govaerts and M Campillo
    Wiley-VCH Verlag GmbH & Co. KGaA 183-203 (2006).
    DOI: 10.1002/3527608249.ch10


  • An activation switch in the rhodopsin family of G protein-coupled receptors: the thyrotropin receptor E Urizar, S Claeysen, X Deupi, C Govaerts, S Costagliola, G Vassart and L Pardo
    J Biol Chem 280, 17135-17141 (2005).
    DOI: 10.1074/jbc.M414678200
  • Probing the beta 2 adrenoceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists G Swaminath, X Deupi, TW Lee, W Zhu, FS Thian, TS Kobilka and B Kobilka
    J Biol Chem 280, 22165-22171 (2005).
    DOI: 10.1074/jbc.M502352200
  • Conformational plasticity of GPCR binding sites X Deupi, C Govaerts, L Shi, JA Javitch, L Pardo and JA Ballesteros
    Humana Press (Ed.: LA Devi) 363-386 (2005).


  • Ser and Thr residues modulate the conformation of Pro-kinked transmembrane alpha-helices X Deupi, M Olivella, C Govaerts, JA Ballesteros, M Campillo and L Pardo
    Biophys J 86, 105-115 (2004).
    DOI: 10.1016/S0006-3495(04)74088-6


  • Activation of CCR5 by chemokines involves an aromatic cluster between transmembrane helices 2 and 3 C Govaerts, A Bondue, JY Springael, M Olivella, X Deupi, E Le Poul, SJ Wodak, M Parmentier, L Pardo and C Blanpain
    J Biol Chem 278, 1892-1903 (2003).
    DOI: 10.1074/jbc.M205685200


  • Influence of the environment in the conformation of alpha-helices studied by protein database search and molecular dynamics simulations M Olivella, X Deupi, C Govaerts and L Pardo
    Biophys J 82, 3207-3213 (2002).
    DOI: 10.1016/S0006-3495(02)75663-4
  • Design, synthesis and pharmacological evaluation of 5-hydroxytryptamine 1a receptor ligands to explore the three-dimensional structure of the receptor ML Lopez-Rodriguez, B Vicente, X Deupi, S Barrondo, M Olivella, MJ Morcillo, B Behamu, JA Ballesteros, J Salles and L Pardo
    Mol Pharmacol 62, 15-21 (2002).
    DOI: 10.1124/mol.62.1.15


  • Selective hydrolysis of 2,4-diaminopyrimidine systems: a theoretical and experimental insight into an old rule J Teixido, JI Borrell, C Colominas, X Deupi, JL Matallana, JL Falco and B Martinez-Teipel
    J Org Chem 66, 192-199 (2001).
    DOI: 10.1021/jo0056390
  • The TxP motif in the second transmembrane helix of CCR5. A structural determinant of chemokine-induced activation C Govaerts, C Blanpain, X Deupi, S Ballet, JA Ballesteros, SJ Wodak, G Vassart, L Pardo and M Parmentier
    J Biol Chem 276, 13217-13225 (2001).
    DOI: 10.1074/jbc.M011670200


  • Serine and threonine residues bend alpha-helices in the chi(1) = g- conformation JA Ballesteros, X Deupi, M Olivella, EE Haaksma and L Pardo
    Biophys J 79, 2754-2760 (2000).
    DOI: 10.1016/S0006-3495(00)76514-3