Dr. Xiaodan Li

All living cells are enveloped by a lipid bilayer called the cell membrane. The cell membrane controls the transport of chemicals and signals from the cytoplasm to the extracellular space, and vice versa, using specific membrane proteins embedded in the lipid bilayer. We are interesting on the structural aspects of channels and receptors and study them by diffraction methods using 3D and 2D crystals.

2D membrane protein crystals grow in the lipid bilayer and form mainly by hydrophobic interactions. 2D crystals have the advantage that the lipid-associated conformations of the membrane protein, due to the no crystal packing at the z-direction, therefore unlikely to adapt conformations which is less-like biological relevant. In addition, ligand with hydrophobic properties can free diffusion within the membrane bilayer. Freedom on the third dimension such as open and closed state of an ion channel can be detected, analyzed and compared to 3D structures obtained in the absence of lipids. Small size 2D-nanocrystals are easily obtained in the presence of ligands, pharmaceutical agents and regulatory nannobodies. The obtained structures of such membrane proteins will provide an important framework for functional characterization and for the identification of potential drug target sites including allosteric sides embedded into the lipid bilayer. We have made progress in terms of obtaining first 3D-structure of 2D crystals of a voltage-gated channel using cryo-EM and 4Å diffraction images from bacteriorhodopsin 2D crystals using X-ray free-lectron laser at LCLS, USA. 2D@FEL will allow studying the dynamic of the membrane protein in lipid bilayer at room temperature.

Our structural studies are complemented by biochemical and genetic analysis. We are collaborating with scientists from academia and from industry at the national and the international level. Being at the Paul Scherrer Institut, the future-host for SwissFEL, we are actively participating in the development of cutting-edge technologies for studying dynamics of membrane proteins using XFEL.

Guo,Haojie Dr.
Postdoc

He,Xiaoqin Dr.
Postdoc

Meury,Marcel Dr.
Postdoc

Rheinberger,Jan
Ph.D. Student

Schärer,Martin
Ph.D. Student

2021

2020

2019

2018

• 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

2017

• Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C Benoit RM, Schaerer MA, Wieser MM, Li X, Frey D, Kammerer RA
  Scientific Reports 7, 43588 (2017).
  DOI: 10.1038/srep43588

2015

• 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
• 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

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
• A Type IV Translocated Legionella Cysteine Phytase Counteracts Intracellular Growth Restriction by Phytate Weber Stephen, Stirnimann Christian U, Wieser Mara, Frey Daniel, Meier Roger, Engelhardt Sabrina, Li Xiaodan, Capitani Guido, Kammerer Richard A, Hilbi Hubert
  JOURNAL OF BIOLOGICAL CHEMISTRY 289, 34175-34188 (2014).
  DOI: 10.1074/jbc.M114.592568
• 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

2013

• 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

2011

• Crystal structure of the GlnZ-DraG complex reveals a different form of P-II-target interaction Rajendran C, Gerhardt ECM, Bjelic S, Gasperina A, Scarduelli M, Pedrosa FO, Chubatsu LS, Merrick M, Souza EM, Winkler FK, Huergo LF, Li XD
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108, 18972 (2011).
  DOI: 10.1073/pnas.1108038108
• Quaternary Structure of the Oxaloacetate Decarboxylase Membrane Complex and Mechanistic Relationships to Pyruvate Carboxylases Balsera M, Buey RM, Li XD
  JOURNAL OF BIOLOGICAL CHEMISTRY 286, 9457 (2011).
  DOI: 10.1074/jbc.M110.197442

2010

• A New P-II Protein Structure Identifies the 2-Oxoglutarate Binding Site Truan D, Huergo LF, Chubatsu LS, Merrick M, Li XD, Winkler FK
  JOURNAL OF MOLECULAR BIOLOGY 400, 531 (2010).
  DOI: 10.1016/j.jmb.2010.05.036

2008

• Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization Kawamura H, Li XJ, Goishi K, van Meeteren LA, Jakobsson L, Cebe-Suarez S, Shimizu A, Edholm D, Ballmer-Hofer K, Kjellen L, Klagsbrun M, Claesson-Welsh L
  BLOOD 112, 3638 (2008).
  DOI: 10.1182/blood-2007-12-125856
• Orf virus VEGF-E NZ2 promotes paracellular NRP-1/VEGFR-2 coreceptor assembly via the peptide RPPR Cebe-Suarez P, Grunewald FS, Jaussi R, Li XJ, Claesson-Welsh L, Spillmann D, Mercer AA, Prota AE, Ballmer-Hofer K
  FASEB JOURNAL 22, 3078 (2008).
  DOI: 10.1096/fj.08-107219

2007

• Structural and mechanistic aspects of Amt/Rh proteins Javelle A, Lupo D, Li X, Merrick M, Chami M, Ripoche P, Winkler FK
  JOURNAL OF STRUCTURAL BIOLOGY 158, 472 (2007).
  DOI: 10.1016/j.jsb.2007.01.004
• The 1.3-A resolution structure of nitrosomas erropea Rh50 and mechanistic implications for NH3 transport by Rhesus family proteins Lupo D, Li XD, Durand A, Tomizaki T, Cherif-zahar B, Matassi G, Merrik M, Winkler FK
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 50, 577 (2007).
• The crystal structure of the Escherichia coli AmtB-GlnK complex reveals how GlnK regulates the ammonia channel Conroy MJ, Durand A, Lupo D, Li XD, Bullough PA, Winkler FK, Merrick M
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104, 1213 (2007).
  DOI: 10.1073/pnas.0610348104

2006

• Structural and functional insights into the AmtB/Mep/Rh protein family Li XD, Lupo D, Zheng L, Winkler F
  TRANSFUSION CLINIQUE ET BIOLOGIQUE 13, 65 (2006).
  DOI: 10.1016/j.tracli.2006.02.014