Xiao-Dan Li,   PhD	Ammonium-conducting channel from AmtB ( Zheng et al. , PNAS 101 (49), 17090 - 17095 (2004))

Membrane Protein Group

Membrane proteins are essential players in molecular transport and signal transduction across biological membranes. The focus of our research is the X-ray crystallographic structure determination of selected such proteins to arrive at a detailed understanding of their function. Important questions concern the structural basis of substrate specificity, interactions with other regulatory or effector proteins and the nature of different conformational states related for example to ligand- or voltage-induced gating of ion channels.

For protein expression we use primarily E. coli but we also have established a number of eukaryotic expression systems. Functional assays of the wild-type or mutant proteins are carried out both in vivo and in vitro. Cellular assays are usually done in collaboration with external expert groups. For in vitro assays we reconstitute the purified proteins into liposomes or planar lipid bilayers. We closely cooperate with the Bio-nanotechnology group to develop a general assay device using nanopores.

Main Projects
(carried out with the support of the NCCR Structural Biology)

• 1. Ammonia channels of the Mep/Amt/Rh family
• 2. Ion channels (voltage- and ligand-gated)
• 3. Intramembrane cleaving proteases

Group Members

Selected Publications

Li, XD, Huergo LF, Gasperina A. Pedrosa FO, Merrick M, Winkler FK (2009)
Crystal structure of dinitrogenase reductase activating glycohydrolase (DRAG) reveals conservation in the ADP-ribosylhydrolase fold and specific features in the ADP-ribose
binding pocket.
J Mol Biol. in press (2009)

Lupo D, Li XD, Durand A, Tomizaki T, Cherif-Zahar B, Matassi G, Merrick M, Winkler FK
The 1.3 Å resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH₃ transport by Rhesus family proteins.
Proc Natl Acad Sci USA 104(49), 19303 - 19308 (2007)

Javelle A, Lupo D, Li XD, Merrick M, Chami M, Ripoche P, Winkler FK
Structural and mechanistic aspects of Amt/Rh proteins.
J Struct  Biol. 158(3), 472 - 481(2007)

Conroy MJ, Durand A, Lupo D, Li XD, Bullough PA, Winkler FK, Merrick M.
Regulating the Escherichia coli ammonia channel: the crystal structure of the AmtB-GlnK complex.
Proc Natl Acad Sci USA 104(4), 1213 - 1218 (2007)

Studer R, Dahinden P, Wang WW, Auchli Y, Li XD, Dimroth P.
Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase Na+ pump from Vibrio cholerae.
J Mol Biol. 367(2), 547 - 557 (2007)

Javelle A, Lupo D, Zheng L, Li XD, Winkler FK, Merrick M.
An unusual twin-his arrangement in the pore of ammonia channels is essential for substrate conductance.
J Biol Chem. 281(51), 39492 - 39498 (2006)

Li XD, Lupo D, Zheng L, Winkler FK.
Structural and functional insights into the AmtB/Mep/Rh protein family.
Transfus Clin Biol. 13(1-2):65 -69 (2006)

Marquardt T, Kostrewa D, Balakrishnan R., Gasperina A., Kambach C., Podjarny A.,
Winkler F.K., Balendiran G.K., Li X.-D. High-resolution Crystal Structure of AKR11C1 from Bacillus halodurans: a NADPH-dependent 4-Hydroxy-2,3-trans-nonenal Reductase.
JMB 354 (2), 304 - 316 (2005).

Zheng L, Kostrewa D, Bernèche S, Winkler FK and Li XD. The mechanism of ammonia transport based on the crystal structure of AmtB of E. coli.
PNAS 101(49), 17090-17095 (2004).

Wang DN, Safferling M, Lemieux MJ, Griffith H, Chen Y, Li XD. Practical aspects of overexpressing bacterial secondary membrane transporters for structural studies. Biochim Biophys Acta.1610(1), 23-36 (2003).

Lemieux MJ, Song J, Kim MJ, Huang Y, Villa A, Auer M, Li XD, Wang DN. Three-dimensional crystallization of the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily. Protein Sci. 12(12), 2748-2756 (2003).

Li XD, Villa A, Gownley C, Kim MJ, Song J, Auer M, Wang DN. Monomeric state and ligand binding of recombinant GABA transporter from Escherichia coli. FEBS Lett. 494(3), 165-169 (2001).

Contact Address

Xiao-Dan Li
Paul Scherrer Institut
Structural Biology Group
Biomolecular Research
Life Sciences Department
OFLC/104
CH-5232 Villigen PSI
Switzerland

Phone: +41-56-310-4469
Fax: +41-56-310-5288