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.

• 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
• Resolution extension by image summing in serial femtosecond crystallography of two-dimensional membrane-protein crystals Casadei Cecilia M, Tsai C, Barty A, Hunter Mark S, Zatsepin Nadia A, Padeste C, Capitani G, Benner WHenry, Boutet S, Hau-Riege Stefan P, Kupitz C, Messerschmidt M, Ogren John I, Pardini T, Rothschild Kenneth J, Sala L, Segelke B, Williams Garth J, Evans James E, Li X, Coleman M, Pedrini B, Frank M
  IUCRJ 5, 103 (2018).
  DOI: 10.1107/S2052252517017043

• Structural biology Signalling under the microscope Tsai ChingJu, Standfuss Joerg, Glaeser Robert M
  NATURE 546, 36-37 (2017).
  DOI: 10.1038/nature22491

• 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

• Low-Z polymer sample supports for fixed-target serial femtosecond X-ray crystallography Feld Geoffrey K, Heymann Michael, Benner W Henry, Pardini Tommaso, Tsai ChingJu, Boutet Sebastien, Coleman Matthew A, Hunter Mark S, Li Xiaodan, Messerschmidt Marc, Opathalage Achini, Pedrini Bill, Williams Garth J, Krantz Bryan A, Fraden Seth, Hau-Riege Stefan, Evans James E, Segelke Brent W, Frank Matthias
  JOURNAL OF APPLIED CRYSTALLOGRAPHY 48, 1072-1079 (2015).
  DOI: 10.1107/S1600576715010493
• 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

• 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
• 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

• 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