Biochemistry and Molecular Biology
Faculty of Medicine
University of Marseilles, France, 1990, BSc
University of Marseilles, France, 1994, PhD
Dartmouth Medical School, USA, 1998, Postdoctoral Fellow
CNRS-University of Paris-Sud, France, 2004,
Principle Investigator
phone: 6048225975
phone: 6048225245
Life Sciences Centre, Office 5407
2350 Health Sciences Mall
Vancouver, BC V6T 1Z3

Investigating membrane protein function and oligomerization with Nanodiscs.

The nanodisc is a model membrane system useful to study membrane proteins. The nanodisc defines a small patch of lipid bilayer (~ 10-12 nm in diameter) stabilized by two amphipathic proteins, termed membrane scaffold proteins (MSPs). The two MSPs wrap around the hydrophobic core of the lipids, effectively creating a water-soluble disc of membrane. The nanodisc is a particularly attractive option for studying membrane proteins, especially in the context of ligand-receptor interactions. Analyze of membrane proteins in nanodiscs have significant advantages over liposome because the particles are small, homogeneous and water-soluble. In addition, biochemical and biophysical methods normally reserved for soluble proteins can be applied, and from either side of the membrane. Various membrane transporters are being studied in the laboratory using the nanodiscs – the SecYEG protein-conducting channel, the MalFGK maltose transporter and the FhuA outer membrane porin responsible for iron uptake. We are also using nanodiscs in a proteomics approach to identify and analyze proteins bound at the surface of various type of cell membranes.

Dalal, K., Chan, C.S., Sligar, S.G., and Duong, F. (2012) Two copies of the SecY channel are necessary to activate the SecA translocation ATPase. Submitted.

Zhang, X.X., Chan, C.S., Bao, H., Fang, Y., Foster, L.J., and Duong, F. (2011). Nanodiscs and SILAC-Based Mass Spectrometry to Identify a Membrane Protein Interactome. J. Proteome Res. In press.

Dalal, K., and Duong, F. (2011). The SecY complex: conducting the orchestra of protein translocation. Trends Cell Biol. 9, 506-514.

Dalal, K., Bao, H., and Duong, F. (2010). Modulation of the SecY channel permeability by pore mutations and trivalent cations. Channels (Austin) 2, 83-86.

Dalal, K., and Duong, F. (2010). Reconstitution of the SecY translocon in nanodiscs. Methods Mol. Biol. 145-156.

Gold, V.A., Robson, A., Bao, H., Romantsov, T., Duong, F., and Collinson, I. (2010). The action of cardiolipin on the bacterial translocon. Proc. Natl. Acad. Sci. U. S. A. 22, 10044-10049.

Dalal, K., and Duong, F. (2009). The SecY complex forms a channel capable of ionic discrimination. EMBO Rep. 7, 762-768.

Dalal, K., Nguyen, N., Alami, M., Tan, J., Moraes, T.F., Lee, W.C., Maurus, R., Sligar, S.S., Brayer, G.D., and Duong, F. (2009). Structure, binding, and activity of Syd, a SecY-interacting protein. J. Biol. Chem. 12, 7897-7902.

Duong, F. (2007). Cell biology: fraternal twins. Nature 7137, 741-743.

Alami, M., Dalal, K., Lelj-Garolla, B., Sligar, S.G., and Duong, F. (2007). Nanodiscs unravel the interaction between the SecYEG channel and its cytosolic partner SecA. EMBO J. 8, 1995-2004.

Maillard, A.P., Lalani, S., Silva, F., Belin, D., and Duong, F. (2007). Deregulation of the SecYEG translocation channel upon removal of the plug domain. J. Biol. Chem. 2, 1281-1287.

Gold, V.A., Duong, F., and Collinson, I. (2007). Structure and function of the bacterial Sec translocon. Mol. Membr. Biol. 5-6, 387-394.

Tam, P.C., Maillard, A.P., Chan, K.K., and Duong, F. (2005). Investigating the SecY plug movement at the SecYEG translocation channel. EMBO J. 19, 3380-3388.

Tziatzios, C., Schubert, D., Lotz, M., Gundogan, D., Betz, H., Schagger, H., Haase, W., Duong, F., and Collinson, I. (2004). The bacterial protein-translocation complex: SecYEG dimers associate with one or two SecA molecules. J. Mol. Biol. 3, 513-524.

Eichler, J., and Duong, F. (2004). Break on through to the other side–the Sec translocon. Trends Biochem. Sci. 5, 221-223.

Duong, F. (2003). Binding, activation and dissociation of the dimeric SecA ATPase at the dimeric SecYEG translocase. EMBO J. 17, 4375-4384.

Bessonneau, P., Besson, V., Collinson, I., and Duong, F. (2002). The SecYEG preprotein translocation channel is a conformationally dynamic and dimeric structure. EMBO J. 5, 995-1003.

Collinson, I., Breyton, C., Duong, F., Tziatzios, C., Schubert, D., Or, E., Rapoport, T., and Kuhlbrandt, W. (2001). Projection structure and oligomeric properties of a bacterial core protein translocase. EMBO J. 10, 2462-2471.

Duong, F., Bonnet, E., Geli, V., Lazdunski, A., Murgier, M., and Filloux, A. (2001). The AprX protein of Pseudomonas aeruginosa: a new substrate for the Apr type I secretion system. Gene 1-2, 147-153.

Duong, F., and Wickner, W. (1999). The PrlA and PrlG phenotypes are caused by a loosened association among the translocase SecYEG subunits. EMBO J. 12, 3263-3270.

Duong, F., and Wickner, W. (1998). Sec-dependent membrane protein biogenesis: SecYEG, preprotein hydrophobicity and translocation kinetics control the stop-transfer function. EMBO J. 3, 696-705.

Duong, F., Eichler, J., Price, A., Leonard, M.R., and Wickner, W. (1997). Biogenesis of the gram-negative bacterial envelope. Cell 5, 567-573.

Duong, F., and Wickner, W. (1997). Distinct catalytic roles of the SecYE, SecG and SecDFyajC subunits of preprotein translocase holoenzyme. EMBO J. 10, 2756-2768.

Duong, F., and Wickner, W. (1997). The SecDFyajC domain of preprotein translocase controls preprotein movement by regulating SecA membrane cycling. EMBO J. 16, 4871-4879.

Price, A., Economou, A., Duong, F., and Wickner, W. (1996). Separable ATPase and membrane insertion domains of the SecA subunit of preprotein translocase. J. Biol. Chem. 49, 31580-31584.

Duong, F., Lazdunski, A., and Murgier, M. (1996). Protein secretion by heterologous bacterial ABC-transporters: the C-terminus secretion signal of the secreted protein confers high recognition specificity. Mol. Microbiol. 3, 459-470.

Duong, F., Soscia, C., Lazdunski, A., and Murgier, M. (1994). The Pseudomonas fluorescens lipase has a C-terminal secretion signal and is secreted by a three-component bacterial ABC-exporter system. Mol. Microbiol. 6, 1117-1126.