Research by Gebhard Schertler

Class A G protein-coupled receptor (GPCRs) transduce extracellular signals across the cell membrane by activating cytoplasmic-bound heterotrimeric GTP binding proteins (G proteins), which, in turn, modulate the activity of downstream effector proteins. Despite the physiological and pharmacological relevance of GPCRs, the structural basis of ligand efficacy and receptor activation, and how these elements translate into cytoplasmic trafficking and cellular response still remain elusive. In the Laboratory for Biomolecular Research we integrate data from structural biology, molecular biology, cellular biology and structural bioinformatics to study the molecular basis of GPCR function. Specifically, we aim to obtain the crystal structure of the complexes between GPCRs and their cytoplasmic partners, the centerpieces that connect extracellular stimuli to intracellular signals. In addition, we plan to compare the profile of activated signaling molecules with their dynamic intracellular localization pattern to learn how receptor activation translates into specific pathways of cellular signaling. Combination of the data resulting from the study of different Class A GPCRs will allow us to obtain a global picture of GPCR signaling. Our goal is to link receptor structure, cellular biological data and pharmacological results to physiological function.

Representative publications

Backbone NMR reveals allosteric signal transduction networks in the beta 1-adrenergic receptor.
Isogai S, Deupi X, Opitz C, Heydenreich FM, Tsai CJ, Brueckner F, Schertler GF, Veprintsev DB, Grzesiek S.
Nature. 2016;530(7589):237-41.

Molecular signatures of G-protein-coupled receptors
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM.
Nature 2013;494(7436):185-94

The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor.
Warne T, Moukhametzianov R, Baker JG, Nehmé R, Edwards PC, Leslie AG, Schertler GF, Tate CG.
Nature. 2011;469(7329):241-4.

The structural basis of agonist-induced activation in constitutively active rhodopsin.
Standfuss J, Edwards PC, D'Antona A, Fransen M, Xie G, Oprian DD, Schertler GF.
Nature. 2011;471(7340):656-60.

Publications

2016

  • A three-dimensional movie of structural changes in bacteriorhodopsin Nango Eriko, Royant Antoine, Kubo Minoru, Nakane Takanori, Wickstrand Cecilia, Kimura Tetsunari, Tanaka Tomoyuki, Tono Kensuke, Song Changyong, Tanaka Rie, Arima Toshi, Yamashita Ayumi, Kobayashi Jun, Hosaka Toshiaki, Mizohata Eiichi, Nogly Przemyslaw, Sugahara Michihiro, Nam Daewoong, Nomura Takashi, Shimamura Tatsuro, Im Dohyun, Fujiwara Takaaki, Yamanaka Yasuaki, Jeon Byeonghyun, Nishizawa Tomohiro, Oda Kazumasa, Fukuda Masahiro, Andersson Rebecka, Bath Petra, Dods Robert, Davidsson Jan, Matsuoka Shigeru, Kawatake Satoshi, Murata Michio, Nureki Osamu, Owada Shigeki, Kameshima Takashi, Hatsui Takaki, Joti Yasumasa, Schertler Gebhard, Yabashi Makina, Bondar AnaNicoleta, Standfuss Jorg, Neutze Richard, Iwata So
    SCIENCE 354, 1552-1557 (2016).
    DOI: 10.1126/science.aah3497
  • Addendum to Three-dimensional mass density mapping of cellular ultrastructure by ptychographic X-ray nanotomography [J. Struct. Biol. 192 (2015) 461-469] Diaz A, Malkova B, Holler M, Guizar-Sicairos M, Lima E, Panneels V, Pigino G, Bittermann A, Wettstein L, Tomizaki T, Bunk O, Schertler G, Ishikawa T, Wepf R, Menzel A
    JOURNAL OF STRUCTURAL BIOLOGY 193, 83 (2016).
    DOI: 10.1016/j.jsb.2015.12.003
  • Backbone NMR reveals allosteric signal transduction networks in the beta1-adrenergic receptor Isogai S, Deupi X, Opitz C, Heydenreich Franziska M, Tsai C, Brueckner F, Schertler Gebhard FX, Veprintsev Dmitry B, Grzesiek S
    NATURE 530, 237 (2016).
    DOI: 10.1038/nature16577
  • Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis Chakrabarti Kalyan S, Agafonov Roman V, Pontiggia F, Otten R, Higgins Matthew K, Schertler Gebhard FX, Oprian Daniel D, Kern D
    CELL REPORTS 14, 32 (2016).
    DOI: 10.1016/j.celrep.2015.12.010
  • Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region Venkatakrishnan AJ, Deupi X, Lebon G, Heydenreich Franziska M, Flock T, Miljus T, Balaji S, Bouvier M, Veprintsev Dmitry B, Tate Christopher G, Schertler G FX, Babu MMadan
    NATURE 536, 484 (2016).
    DOI: 10.1038/nature19107
  • Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography Nogly P, Panneels V, Nelson G, Gati C, Kimura T, Milne C, Milathianaki D, Kubo M, Wu W, Conrad C, Coe J, Bean R, Zhao Y, Båth P, Dods R, Harimoorthy R, Beyerlein Kenneth R, Rheinberger J, James D, DePonte D, Li C, Sala L, Williams Garth J, Hunter Mark S, Koglin Jason E, Berntsen P, Nango E, Iwata S, Chapman Henry N, Fromme P, Frank M, Abela R, Boutet S, Barty A, White Thomas A, Weierstall U, Spence J, Neutze R, Schertler G, Standfuss J
    NATURE COMMUNICATIONS 7, 12314 (2016).
    DOI: 10.1038/ncomms12314
  • Structural role of the T94I rhodopsin mutation in congenital stationary night blindness Singhal Ankita, Guo Ying, Matkovic Milos, Schertler Gebhard, Deupi Xavier, Yan Elsa C Y, Standfuss Joerg
    EMBO REPORTS 17, 1431-1440 (2016).
    DOI: 10.15252/embr.201642671
  • Three-dimensional mass density mapping of cellular ultrastructure by ptychographic X-ray nanotomography (vol 192, pg 461, 2015) Diaz Ana, Malkova Barbora, Holler Mirko, Guizar-Sicairos Manuel, Lima Enju, Panneels Valerie, Pigino Gaia, Bittermann Anne Greet, Wettstein Larissa, Tomizaki Takashi, Bunk Oliver, Schertler Gebhard, Ishikawa Takashi, Wepf Roger, Menzel Andreas
    JOURNAL OF STRUCTURAL BIOLOGY 193, 83-83 (2016).
    DOI: 10.1016/j.jsb.2015.12.003
Top

2015

  • Batch crystallization of rhodopsin for structural dynamics using an X-ray free-electron laser Wu W, Nogly P, Rheinberger J, M Kick L, Gati C, Nelson G, Deupi X, Standfuss J, Schertler G, Panneels V
    ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS 71, 856 (2015).
    DOI: 10.1107/S2053230X15009966
  • Conformational activation of visual rhodopsin in native disc membranes Malmerberg E, Bovee-Geurts PHM, Katona G, Deupi X, Arnlund D, Wickstrand C, Johansson LC, Westenhoff S, Nazarenko E, Schertler GFX, Menzel A, de Grip WJ, Neutze R
    Science Signaling 8, ra26 (2015).
    DOI: 10.1126/scisignal.2005646
  • GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1?2 September 2014 Heifetz A, Schertler Gebhard FX, Seifert R, Tate Christopher G, Sexton Patrick M, Gurevich Vsevolod V, Fourmy D, Cherezov V, Marshall Fiona H, Storer RIan, Moraes I, Tikhonova Irina G, Tautermann Christofer S, Hunt P, Ceska T, Hodgson S, Bodkin Mike J, Singh S, Law Richard J, Biggin Philip C
    Naunyn-Schmiedeberg's Archives of Pharmacology 388, 883 (2015).
    DOI: 10.1007/s00210-015-1111-8
  • Large scale expression and purification of the rat 5-HT2c receptor He X, Robertson N, Jazayeri A, Gasperina A, Schertler G, Li X
    PROTEIN EXPRESSION AND PURIFICATION 106, 1 (2015).
    DOI: 10.1016/j.pep.2014.10.010
  • Lipidic cubic phase serial millisecond crystallography using synchrotron radiation Nogly Przemyslaw, James Daniel, Wang Dingjie, White Thomas A, Zatsepin Nadia, Shilova Anastasya, Nelson Garrett, Liu Haiguang, Johansson Linda, Heymann Michael, Jaeger Kathrin, Metz Markus, Wickstrand Cecilia, Wu Wenting, Bath Petra, Berntsen Peter, Oberthuer Dominik, Panneels Valerie, Cherezov Vadim, Chapman Henry, Schertler Gebhard, Neutze Richard, Spence John, Moraes Isabel, Burghammer Manfred, Standfuss Joerg, Weierstall Uwe
    IUCRJ 2, 168-176 (2015).
    DOI: 10.1107/S2052252514026487
  • Membrane protein structural biology using X-ray free electron lasers Neutze R, Brändén G, Schertler G
    CURRENT OPINION IN STRUCTURAL BIOLOGY 33, 115 (2015).
    DOI: 10.1016/j.sbi.2015.08.006
  • Probing Galpha_i1 protein activation at single?amino acid resolution Sun D, Flock T, Deupi X, Maeda S, Matkovic M, Mendieta S, Mayer D, Dawson R, Schertler G, Babu M, Veprintsev D
    NATURE STRUCTURAL & MOLECULAR BIOLOGY 22, 686 (2015).
    DOI: 10.1038/nsmb.3070
  • Rhodopsin on Tracks: New Ways to Go in Signaling Schertler Gebhard FX
    STRUCTURE 23, 606 (2015).
    DOI: 10.1016/j.str.2015.03.008
  • Three-dimensional mass density mapping of cellular ultrastructure by ptychographic X-ray nanotomography Diaz A, Malkova B, Holler M, Guizar-Sicairos M, Lima E, Panneels V, Pigino G, Bittermann A, Wettstein L, Tomizaki T, Bunk O, Schertler G, Ishikawa T, Wepf R, Menzel A
    JOURNAL OF STRUCTURAL BIOLOGY 192, 461 (2015).
    DOI: 10.1016/j.jsb.2015.10.008
  • Time-resolved structural studies with serial crystallography: A new light on retinal proteins Panneels Valerie, Wu Wenting, Tsai ChingJu, Nogly Przemek, Rheinberger Jan, Jaeger Kathrin, Cicchetti Gregor, Gati Cornelius, Kick Leonhard M, Sala Leonardo, Capitani Guido, Milne Chris, Padeste Celestino, Pedrini Bill, Li XiaoDan, Standfuss Joerg, Abela Rafael, Schertler Gebhard
    STRUCTURAL DYNAMICS 2, 041718 (2015).
    DOI: 10.1063/1.4922774
Top

2014

  • 7 angstrom resolution in protein two-dimensional-crystal X-ray diffraction at Linac Coherent Light Source Pedrini Bill, Tsai Ching-Ju, Capitani Guido, Padeste Celestino, Hunter Mark S, Zatsepin Nadia A, Barty Anton, Benner W Henry, Boutet Sebastien, Feld Geoffrey K, Hau-Riege Stefan P, Kirian Richard A, Kupitz Christopher, Messerschmitt Marc, Ogren John I, Pardini Tommaso, Segelke Brent, Williams Garth J, Spence John C H, Abela Rafael, Coleman Matthew, Evans James E, Schertler Gebhard F X, Frank Matthias, Li Xiao-Dan
    PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES 369, UNSP 20130500 (2014).
    DOI: 10.1098/rstb.2013.0500
  • Crystallization Scale Preparation of a Stable GPCR Signaling Complex between Constitutively Active Rhodopsin and G-Protein Garriga P, Maeda S, Sun D, Singhal A, Foggetta M, Schmid G, Standfuss J, Hennig M, Dawson Roger JP, Veprintsev Dmitry B, Schertler Gebhard FX
    PLOS ONE 9, e98714 (2014).
    DOI: 10.1371/journal.pone.0098714
  • Femtosecond X-ray diffraction from two-dimensional protein crystals Frank Matthias, Carlson David B, Hunter Mark S, Williams Garth J, Messerschmidt Marc, Zatsepin Nadia A, Barty Anton, Benner W Henry, Chu Kaiqin, Graf Alexander T, Hau-Riege Stefan P, Kirian Richard A, Padeste Celestino, Pardini Tommaso, Pedrini Bill, Segelke Brent, Seibert M Marvin, Spence John C H, Tsai ChingJu, Lane Stephen M, Li XiaoDan, Schertler Gebhard, Boutet Sebastien, Coleman Matthew, Evans James E
    IUCRJ 1, 95-100 (2014).
    DOI: 10.1107/S2052252514001444
  • Molecular mechanism of phosphorylation-dependent arrestin activation Ostermaier M, Schertler G, Standfuss J
    CURRENT OPINION IN STRUCTURAL BIOLOGY 29, 143 (2014).
    DOI: 10.1016/j.sbi.2014.07.006
  • Retinal proteins ? You can teach an old dog new tricks Heberle J, Deupi X, Schertler G
    Biochimica et Biophysica Acta (BBA) - Bioenergetics 1837, 531 (2014).
    DOI: 10.1016/j.bbabio.2014.02.019
  • Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A Benoit Roger M, Frey Daniel, Hilbert Manuel, Kevenaar Josta T, Wieser Mara M, Stirnimann Christian U, McMillan David, Ceska Tom, Lebon Florence, Jaussi Rolf, Steinmetz Michel O, Schertler Gebhard F X, Hoogenraad Casper C, Capitani Guido, Kammerer Richard A
    NATURE 505, 108-+ (2014).
    DOI: 10.1038/nature12732
  • The 2.1 Å Resolution Structure of Cyanopindolol-Bound ?1-Adrenoceptor Identifies an Intramembrane Na+ Ion that Stabilises the Ligand-Free Receptor van Veen Hendrik W, Miller-Gallacher Jennifer L, Nehmé R, Warne T, Edwards Patricia C, Schertler Gebhard FX, Leslie Andrew GW, Tate Christopher G
    PLOS ONE 9, e92727 (2014).
    DOI: 10.1371/journal.pone.0092727
Top

2013

  • Constitutively active rhodopsin mutants causing night blindness are effectively phosphorylated by GRKs but differ in arrestin-1 binding Vishnivetskiy SergeyA, Ostermaier Martin K, Singhal A, Panneels V, Homan Kristoff T, Glukhova A, Sligar Stephen G, Tesmer John JG, Schertler Gebhard FX, Standfuss J, Gurevich Vsevolod V
    CELLULAR SIGNALLING 25, 2155 (2013).
    DOI: 10.1016/j.cellsig.2013.07.009
  • Insights into congenital stationary night blindness based on the structure of G90D rhodopsin Singhal Ankita, Ostermaier Martin K, Vishnivetskiy Sergey A, Panneels Valerie, Homan Kristoff T, Tesmer John J G, Veprintsev Dmitry, Deupi Xavier, Gurevich Vsevolod V, Schertler Gebhard F X, Standfuss Joerg
    EMBO REPORTS 14, 520-526 (2013).
    DOI: 10.1038/embor.2013.44
  • Molecular signatures of G-protein-coupled receptors Venkatakrishnan A J, Deupi Xavier, Lebon Guillaume, Tate Christopher G, Schertler Gebhard F, Babu M Madan
    NATURE 494, 185-194 (2013).
    DOI: 10.1038/nature11896
  • Production of GPCR and GPCR complexes for structure determination Maeda S, Schertler G
    CURRENT OPINION IN STRUCTURAL BIOLOGY 23, 381 (2013).
    DOI: 10.1016/j.sbi.2013.04.006
  • Structure of beta-Adrenergic Receptors Brueckner Florian, Piscitelli Chayne L, Tsai Ching-Ju, Standfuss Joerg, Deupi Xavier, Schertler Gebhard F X
    G PROTEIN COUPLED RECEPTORS: STRUCTURE 520, 117-151 (2013).
    DOI: 10.1016/B978-0-12-391861-1.00006-X
  • Two Alternative Conformations of a Voltage-Gated Sodium Channel Tsai C, Tani K, Irie K, Hiroaki Y, Shimomura T, McMillan Duncan G, Cook Gregory M, Schertler Gebhard FX, Fujiyoshi Y, Li X
    JOURNAL OF MOLECULAR BIOLOGY 425, 4074 (2013).
    DOI: 10.1016/j.jmb.2013.06.036
Top

2012

  • Conserved activation pathways in G-protein-coupled receptors Deupi X, Standfuss J, Schertler G
    BIOCHEMICAL SOCIETY TRANSACTIONS 40, 383-388 (2012).
    DOI: 10.1042/BST20120001
  • Ligands Stabilize Specific GPCR Conformations: But How? Deupi X, Li XD, Schertler GFX
    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 Deupi X, Edwards P, Singhal A, Nickle B, Oprian D, Schertler G, Standfuss J
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109, 119 (2012).
    DOI: 10.1073/pnas.1114089108

2011

  • ?4D Biology for health and disease? workshop report Abrahams J, Apweiler R, Balling R, Bertero Michela G, Bujnicki Janusz M, Chayen Naomi E, Chène P, Corthals Gary L, Dyl?g T, Förster F, Heck Albert JR, Henderson Peter JF, Herwig R, Jehenson P, Kokalj S, Laue E, Legrain P, Martens L, Migliorini C, Musacchio A, Podobnik M, Schertler Gebhard FX, Schreiber G, Sixma Titia K, Smit August B, Stuart D, Svergun Dmitri I, Taussig Michael J
    New Biotechnology 28, 291 (2011).
    DOI: 10.1016/j.nbt.2010.10.003
  • Adaptation of pineal expressed teleost exo-rod opsin to non-image forming photoreception through enhanced Meta II decay Tarttelin Emma E, Fransen Maikel P, Edwards Patricia C, Hankins Mark W, Schertler Gebhard FX, Vogel R, Lucas Robert J, Bellingham J
    CELLULAR AND MOLECULAR LIFE SCIENCES 68, 3713 (2011).
    DOI: 10.1007/s00018-011-0665-y
  • Membranes Stroud R, Schertler G
    CURRENT OPINION IN STRUCTURAL BIOLOGY 21, 495 (2011).
    DOI: 10.1016/j.sbi.2011.08.001
  • Preparation of an Activated Rhodopsin/Transducin Complex Using a Constitutively Active Mutant of Rhodopsin Xie G, D?Antona Aaron M, Edwards Patricia C, Fransen M, Standfuss J, Schertler Gebhard FX, Oprian Daniel D
    BIOCHEMISTRY 50, 10399 (2011).
    DOI: 10.1021/bi201126r
  • The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor Warne T, Moukhametzianov R, Baker JG, Nehme R, Edwards PC, Leslie AGW, Schertler GFX, Tate CG
    NATURE 469, 241 (2011).
    DOI: 10.1038/nature09746
  • The structural basis of agonist-induced activation in constitutively active rhodopsin Standfuss J, Edwards PC, D'Antona A, Fransen M, Xie GF, Oprian DD, Schertler GFX
    NATURE 471, 656 (2011).
    DOI: 10.1038/nature09795
  • Two distinct conformations of helix 6 observed in antagonist-bound structures of a beta(1)-adrenergic receptor Moukhametzianov R, Warne T, Edwards PC, Serrano-Vega MJ, Leslie AGW, Tate CG, Schertler GFX
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108, 8228 (2011).
    DOI: 10.1073/pnas.1100185108
Top

2010

  • Spial: analysis of subtype-specific features in multiple sequence alignments of proteins Wuster A, Venkatakrishnan AJ, Schertler GFX, Babu MM
    BIOINFORMATICS 26, 2906 (2010).
    DOI: 10.1093/bioinformatics/btq552
  • Tracking G-protein-coupled receptor activation using genetically encoded infrared probes Ye SX, Zaitseva E, Caltabiano G, Schertler GFX, Sakmar TP, Deupi X, Vogel R
    NATURE 464, 1386 (2010).
    DOI: 10.1038/nature08948

2009

  • Engineering G protein-coupled receptors to facilitate their structure determination Tate CG, Schertler GFX
    CURRENT OPINION IN STRUCTURAL BIOLOGY 19, 386 (2009).
    DOI: 10.1016/j.sbi.2009.07.004