Dr. Ching-Ju Tsai

G-protein coupled receptors (GPCRs) are the targets of almost half of today’s pharmaceuticals. They contribute to signal transduction across the cell membrane. GPCRs are activated by extracellular stimuli such as light, hormone, and small ligand, resulting in conformational changes and interaction with a number of signalling and regulatory proteins including G proteins, kinases and arrestins. The first step in GPCR activation leads to conformational changes which trigger interaction with G proteins. There are four main subtypes of G proteins, each inducing specific signalling pathways. Most GPCRs can couple to more than one G-protein subtype, and therefore it is fundamental to understand GPCR signalling by studying the coupling specificity between G protein and GPCRs. We aim to decipher the mechanism by which this selectivity is achieved. To do so, we use X-ray crystallography, electron cryo-microscopy (cryo-EM) together with biochemical techniques to characterize the molecular mechanism of GPCR signalling complexes.

2024

• Active state structures of a bistable visual opsin bound to G proteins Tejero O, Pamula F, Koyanagi M, Nagata T, Afanasyev P, Das I, Deupi X, Sheves M, Terakita A, Schertler GFX, Rodrigues MJ, Tsai CJ. 
  Nature communications, 15(1 ), 8928 (2024) doi:10.1038/s41467-024-53208-2
  DOI: 10.1038/s41467-024-53208-2
• Activating an invertebrate bistable opsin with the all-trans 6.11 retinal analog Rodrigues MJ, Tejero O, Mühle J, Pamula F, Das I, Tsai CJ, Terakita A, Sheves M, Schertler GFX
  iScience, 26(2), 105928 (2023) Proc Natl Acad Sci U S A, 121(31):e2406814121 (2024)
   DOI: 10.1073/pnas.2406814121

2023

• Ultrafast structural changes direct the first molecular events of vision Gruhl T, Weinert T, Rodrigues MJ, Milne CJ, Ortolani G, Nass K, Nango E, Sen S, Johnson PJM, Cirelli C, Furrer A, Mous S, Skopintsev P, James D, Dworkowski F, Båth P, Kekilli D, Ozerov D, Tanaka R, Glover H, Bacellar C, Brünle S, Casadei CM, Diethelm AD, Gashi D, Gotthard G, Guixà-González R, Joti Y, Kabanova V, Knopp G, Lesca E, Ma P, Martiel I, Mühle J, Owada S, Pamula F, Sarabi D, Tejero O, Tsai CJ, Varma N, Wach A, Boutet S, Tono K, Nogly P, Deupi X, Iwata S, Neutze R, Standfuss J, Schertler G, Panneels V
  Nature, 615(7954), 939–944 (2023)
  DOI: 10.1038/s41586-023-05863-6
• Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region Emmenegger M, De Cecco E, Lamparter D, Jacquat RPB, Riou J, Menges D, Ballouz T, Ebner D, Schneider MM, Morales IC, Doğançay B, Guo J, Wiedmer A, Domange J, Imeri M, Moos R, Zografou C, Batkitar L, Madrigal L, Schneider D, Trevisan C, Gonzalez-Guerra A, Carrella A, Dubach IL, Xu CK, Meisl G, Kosmoliaptsis V, Malinauskas T, Burgess-Brown N, Owens R, Hatch S, Mongkolsapaya J, Screaton GR, Schubert K, Huck JD, Liu F, Pojer F, Lau K, Hacker D, Probst-Müller E, Cervia C, Nilsson J, Boyman O, Saleh L, Spanaus K, von Eckardstein A, Schaer DJ, Ban N, Tsai CJ, Marino J, Schertler GFX, Ebert N, Thiel V, Gottschalk J, Frey BM, Reimann RR, Hornemann S, Ring AM, Knowles TPJ, Puhan MA, Althaus CL, Xenarios I, Stuart DI, Aguzzi A
  iScience, 26(2), 105928 (2023)
  DOI: 10.1016/j.isci.2023.105928

2022

• Preparation of a stable CCL5·CCR5·Gi signaling complex for Cryo-EM analysis Isaikina P, Tsai CJ, Petrovic I, Rogowski M, Dürr AM, Grzesiek S
  Methods in cell biology, 169, 115–141 (2022)
  DOI: 10.1016/bs.mcb.2022.03.00

2021

• Versatile microporous polymer-based supports for serial macromolecular crystallography Martiel I, Beale JH, Karpik A, Huang CY, Vera L, Olieric N, Wranik M, Tsai CJ, Mühle J, Aurelius O, John J, Högbom M, Wang M, Marsh M, Padeste C
  Proceedings of the National Academy of Sciences of the United States of America, 118(31), e2024146118 (2021)
  DOI: 10.1107/S2059798321007324
• High-mass MALDI-MS unravels ligand-mediated G protein-coupling selectivity to GPCRs Wu N, Olechwier AM, Brunner C, Edwards PC, Tsai CJ, Tate CG, Schertler GFX, Schneider G, Deupi X, Zenobi R, Ma P
  Proceedings of the National Academy of Sciences of the United States of America, 118(31), e2024146118 (2021)
  DOI: 10.1073/pnas.2024146118
• Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist Isaikina P, Tsai CJ, Dietz N, Pamula F, Grahl A, Goldie KN, Guixà-González R, Branco C, Paolini-Bertrand M, Calo N, Cerini F, Schertler GFX, Hartley O, Stahlberg H, Maier T, Deupi X, Grzesiek S
  Science advances, 7(25), eabg8685 (2021)
  DOI: 10.1126/sciadv.abg8685
• Biochemical Characterization of GPCR-G Protein Complex Formation Pamula F, Tsai CJ
  Methods in molecular biology (Clifton, N.J.), 2302, 37–48 (2021)
  DOI: 10.1007/978-1-0716-1394-8_3

2020

• GPCR Activation States Induced by Nanobodies and Mini-G Proteins Compared by NMR Spectroscopy Rößler P, Mayer D, Tsai CJ, Veprintsev DB, Schertler GFX, Gossert AD
  Molecules (Basel, Switzerland), 25(24), 5984 (2020)
  DOI: 10.3390/molecules25245984
• Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization Pamula F, Mühle J, Blanc A, Nehmé R, Edwards PC, Tate CG, Tsai CJ
  Journal of visualized experiments, 157, 10.3791/60747 (2020)
  DOI: 10.3791/60747
• Membrane Protein Crystallization Tsai CJ, Schertler GFX
  Structural Biology in Drug Discovery: Methods, Techniques, and Practices: 187-210 (2020)
  DOI: 10.1002/9781118681121.ch9

2019

• Emerging Two-Dimensional Crystallization of Cucurbit[8]uril Complexes: From Supramolecular Polymers to Nanofibers Barrio JD, Liu J, Brady RA, Tan CSY, Chiodini S, Ricci M, Fernández-Leiro R, Tsai CJ, Vasileiadi P, Di Michele L, Lairez D, Toprakcioglu C, Scherman OA
  Journal of the American Chemical Society, 141(36), 14021–14025 (2019)
  DOI: 10.1021/jacs.9b07506
• Cryo-EM structure of the rhodopsin-Gαi-βγ complex reveals binding of the rhodopsin C-terminal tail to the Gβ subunit Tsai CJ, Marino J, Adaixo R, Pamula F, Muehle J, Maeda S, Flock T, Taylor NM, Mohammed I, Matile H, Dawson RJ, Deupi X, Stahlberg H, Schertler G
  eLife, 8, e46041 (2019)
  DOI: 10.7554/eLife.46041
• Structure-factor amplitude reconstruction from serial femtosecond crystallography of two-dimensional membrane-protein crystals Casadei CM, Nass K, Barty A, Hunter MS, Padeste C, Tsai CJ, Boutet S, Messerschmidt M, Sala L, Williams GJ, Ozerov D, Coleman M, Li XD, Frank M, Pedrini B
  IUCrJ, 6(Pt 1), 34–45 (2019)
  DOI: 10.1107/S2052252518014641

2018

• 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(9), eaat7052 (2018).
  DOI: 10.1126/sciadv.aat7052
• Resolution extension by image summing in serial femtosecond crystallography of two-dimensional membrane-protein crystals Casadei CM, Tsai CJ, Barty A, Hunter MS, Zatsepin NA, Padeste C, Capitani G, Benner WH, Boutet S, Hau-Riege SP, Kupitz C, Messerschmidt M, Ogren JI, Pardini T, Rothschild KJ, Sala L, Segelke B, Williams GJ, Evans JE, Li XD, Coleman M, Pedrini B, Frank M
  IUCrJ, 5(Pt 1), 103–117 (2018).
  DOI: 10.1107/S2052252517017043

2017

• Structural biology: Signalling under the microscope Tsai CJ, Standfuss J, Glaeser RM
  Nature, 546(7656), 36–37 (2017).
  DOI: 10.1038/nature22491

2016

• Backbone NMR reveals allosteric signal transduction networks in the beta1-adrenergic receptor Isogai S, Deupi X, Opitz C, Heydenreich FM, Tsai CJ, Brueckner F, Schertler GFX, Veprintsev DB, Grzesiek S
  Nature, 530(7589), 237–241 (2016).
  DOI: 10.1038/nature16577

Pre-2015

• Low-Z polymer sample supports for fixed-target serial femtosecond X-ray crystallography Feld GK, Heymann M, Benner WH, Pardini T, Tsai CJ, Boutet S, Coleman MA, Hunter MS, Li X, Messerschmidt M, Opathalage A, Pedrini B, Williams GJ, Krantz BA, Fraden S, Hau-Riege S, Evans JE, Segelke BW, Frank M
  Journal of Applied Crystallography, 48(4), 1072-1079 (2015).
  DOI: 10.1107/S1600576715010493
• Time-resolved structural studies with serial crystallography: A new light on retinal proteins Panneels V, Wu W, Tsai CJ, Nogly P, Rheinberger J, Jaeger K, Cicchetti G, Gati C, Kick LM, Sala L, Capitani G, Milne C, Padeste C, Pedrini B, Li XD, Standfuss J, Abela R, Schertler G
  Structural dynamics (Melville, N.Y.), 2(4), 041718 (2015).
  DOI: 10.1063/1.4922774
• 7 Å resolution in protein two-dimensional-crystal X-ray diffraction at Linac Coherent Light Source Pedrini B, Tsai CJ, Capitani G, Padeste C, Hunter MS, Zatsepin NA, Barty A, Benner WH, Boutet S, Feld GK, Hau-Riege SP, Kirian RA, Kupitz C, Messerschmitt M, Ogren JI, Pardini T, Segelke B, Williams GJ, Spence JC, Abela R, Coleman M, Evans JE, Schertler GF, Frank M, Li XD
  Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 369(1647), 20130500 (2014).
  DOI: 10.1098/rstb.2013.0500
• Femtosecond X-ray diffraction from two-dimensional protein crystals Frank M, Carlson DB, Hunter MS, Williams GJ, Messerschmidt M, Zatsepin NA, Barty A, Benner WH, Chu K, Graf AT, Hau-Riege SP, Kirian RA, Padeste C, Pardini T, Pedrini B, Segelke B, Seibert MM, Spence JC, Tsai CJ, Lane SM, Li XD, Schertler G, Boutet S, Coleman M, Evans JE
  IUCrJ, 1(Pt 2), 95–100 (2014).
  DOI: 10.1107/S2052252514001444
• Structural interactions between inhibitor and substrate docking sites give insight into mechanisms of human PS1 complexes Li Y, Lu SH, Tsai CJ, Bohm C, Qamar S, Dodd RB, Meadows W, Jeon A, McLeod A, Chen F, Arimon M, Berezovska O, Hyman BT, Tomita T, Iwatsubo T, Johnson CM, Farrer LA, Schmitt-Ulms G, Fraser PE, St George-Hyslop PH
  Structure (London, England : 1993), 22(1), 125–135 (2013).
  DOI: 10.1016/j.str.2013.09.018
• Two alternative conformations of a voltage-gated sodium channel Tsai CJ, Tani K, Irie K, Hiroaki Y, Shimomura T, McMillan DG, Cook GM, Schertler GF, Fujiyoshi Y, Li XD
  Journal of molecular biology, 425(22), 4074–4088 (2013).
  DOI: 10.1016/j.jmb.2013.06.03
• Structure of β-adrenergic receptors Brueckner F, Piscitelli CL, Tsai CJ, Standfuss J, Deupi X, Schertler GF
  Methods in enzymology, 520, 117–151 (2013).
  DOI: 10.1016/B978-0-12-391861-1.00006-X
• Structural asymmetry in a trimeric Na+/betaine symporter, BetP, from Corynebacterium glutamicum Tsai CJ, Khafizov K, Hakulinen J, Forrest LR, Forrest LR, Krämer R, Kühlbrandt W, Ziegler C
  Journal of molecular biology, 407(3), 368–381 (2011).
  DOI: 10.1016/j.jmb.2011.01.028
• Coupling electron cryomicroscopy and X-ray crystallography to understand secondary active transport Tsai CJ, Ziegler C
  Journal of molecular biology, 425(22), 4074–4088 (2010).
  DOI: 10.1016/j.sbi.2010.06.005
• The role of lipids and salts in two-dimensional crystallization of the glycine-betaine transporter BetP from Corynebacterium glutamicum Tsai CJ, Ejsing CS, Shevchenko A, Ziegler C
  Journal of structural biology, 160(3), 275–286 (2007).
  DOI: 10.1016/j.jsb.2007.09.008
• Structure determination of secondary transport proteins by electron crystallography: two-dimensional crystallization of the betaine uptake system BetP Tsai CJ, Ziegler C
  Journal of molecular microbiology and biotechnology, 10(2-4), 197–207 (2005).
  DOI: 10.1159/000091565

Invited Talks

Supervision of PhD Students

Teaching and Courses