Research by 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.

Representative publications

X-ray structure of the mouse serotonin 5-HT3 receptor
Hassaine G, Deluz C, Grasso L, Wyss R, Tol MB, Hovius R, Graff A, Stahlberg H, Tomizaki T, Desmyter A, Moreau C, Li XD, Poitevin F, Vogel, Nury H.
Nature 2014;512(7514):276-281

7Å 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
Philos Trans R Soc Lond B Biol Sci. 2014 369(1647):20130500

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
J Mol Biol. 2013 425(22):4074-8.