Research:

Membrane proteins are key targets for the drug development. Our research centers around studying membrane proteins involved in disease, using X-ray crystallography and other biophysical techniques, to reveal structural, functional and mechanistic details of membrane proteins that could one day aid in the development of new drugs and vaccines targeted towards membrane proteins.

One major focus of the lab is the study of rhomboid intramembrane proteases (peptidases). Rhomboid function has been linked to Parkinson’s disease, breast cancer and parasitic invasion. Our crystal structures of this novel type of protease are providing information on how the rhomboid protease acts to cleave protein targets in the membrane. Using both functional and structural approaches we are focusing on how rhomboid proteases regulate cleavage of their substrates. This information is crucial to assist with de novo drug design.

 

Selected Publications:

Lazareno-Saez C, Arutyunova E., Coquelle, N., Lemieux MJ. (2013) Domain swapping in the cytoplasmic domain of E. coli rhomboid protease. J Mol Biol.  425(7):1127-42.

Brooks, CL, Morrison, M, Lemieux, MJ. (2013) Novel plate screening technique for over-expression assessment of eukaryotic targets expressed in PichiaProtein Science. 21 FEB 2013, DOI: 10.1002/pro.2223.

Sampathkumar P, Mak MW, Withold S,  Guigard E, Kay CM, Lemieux JM. (2012) Quaternary structure analysis of rhomboid intramembrane peptidases reveals a homodimer. BBA Biomembranes. 1818(12):3090-7.

Brooks CL, Lazareno-Saez C, Lamoureux JS, Mak MW, and Lemieux MJ (2011). Insights into substrate gating in H. influenzae rhomboid. J Mol Biol 407:687-697

Lemieux MJ, Fischer SJ, Cherney MM, Bateman KS, and James MN. (2007). The crystal structure of the rhomboid peptidase from Haemophilus influenzae provides insight into intramembrane proteolysis. Proc Natl Acad Sci U S A 104:750-754.

Lemieux MJ, Song J, Kim MJ, Huang Y, Villa A, Auer M, Li XD, and Wang D.N. (2003) Three-dimensional crystallization of the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily. Protein Sci. 12(12):2748-56

Huang Y*, Lemieux MJ*, Song J, Auer M, and Wang DN. (2003) Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science. 301(5633):616-20.*co-authors