University of Toronto Biochemistry

	Gil Privé Professor Ph.D., UCLA, 1988
	MaRS Toronto Medical Discovery Tower Room 4-302 416-581-7541 prive@uhnres.utoronto.ca

Protein Structure and X-Ray Crystallography
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Research Synopsis

Complex between co-repressor peptides and the BCL6 BTB domain.

Crystal structure of PagP, an integral membrane enzyme.

My research centers on the study of protein structure, molecular recognition,
transcriptional repression and membrane protein structure. Most projects have the theme of understanding protein-protein, protein-peptide and protein-lipid interactions at the molecular level and relating this to function. We use biochemical and biophysical techniques, including x-ray crystallography.

Structure and function of the BTB domain
The BTB domain is a protein motif that is found in over 200 different human proteins. Several human BTB-zinc finger proteins, including PLZF and BCL6, are transcriptional repressors that are implicated in development and/or in cancer. We are studying the protein-protein interactions of BTB domains with the objective of developing protein-protein interaction inhibitors to reverse the biological activities of these oncogene products.

Structural biology of membrane proteins
We have projects on determining the structures of integral membrane transporters and enzymes. We are addressing the problem of membrane protein crystallization by developing lipopeptide detergents (LPDs), a fundamentally different class of amphiphile designed specifically for the crystallization of membrane proteins. We are also studying the thermodynamics of membrane protein folding and the fundamental properties of protein-lipid and protein detergent interactions.

Structure and Function of Saposin Proteins
Saposins are small, soluble, non-enzymatic lysosomal proteins required for the breakdown of glycosphingolipids. We have solved crystal structures of of all four human saposins. We are using crystallography, atomic force microscopy and fluorescent methods to study the interactions of saposins with membranes and hydrolase enzymes.

Selected Publications

Ghetu AF, Corcoran CM, Cerhietti L, Bardwell J, Melnick A and Privé GG. Structure of a BCOR Corepressor Peptide in Complex with the BCL6 BTB Domain Dimer. Mol. Cell 29, 384-391 (2008).

Ho DN, Pomroy NC, Cuesta-Seijo JA and Privé GG. Crystal structure of a self-assembling lipopeptide detergent at 1.20 Å. PNAS 105, 12861-12866 (2008).

Michaux C, Pomroy NC and Privé GG.Refolding SDS-denatured proteins by the addition of amphipathic cosolvents. J. Mol. Biol. 375, 1477-1488 (2008).

Parekh SS, Privé GG and Melnick A. Therapeutic targeting of the BCL6 oncogene for diffuse large B-cell lymphomas. Leukemia and Lymphoma. 49, 874-882 (2008).

Alattia JR, Shaw JE, Yip CM, Privé GG.Molecular imaging of membrane interfaces reveals mode of beta-glucosidase activation by saposin C. PNAS 104, 17388-17393 (2007).

Privé GG. Detergents for the stabilization and crystallization of membrane proteins. Methods 41, 388-397 (2007).

Privé GG and Melnick A. Specific peptides for the therapeutic targeting of oncogenes. Curr Opin Genet Dev. 16, 71-77 (2006)

Stogios PJ, Downs GS, Jauhal J, Nandra S and Privé GG.Sequence and structural analysis of BTB proteins.Genome Biology 6, R82 (2005).

Ahn VE, Lo EI, Engel CK, Chen L, Hwang PM, Kay LE, Bishop RE, Privé GG.A hydrocarbon ruler measures palmitate in the enzymatic acylation of endotoxin. EMBO J. 23, 2931-2941 (2004).

Ahmad KF, Melnick A, Lax S, Bouchard D, Liu J, Kiang C, Mayer S, Takahashi S, Licht JD, Privé GG. Mechanism of SMRT Corepressor Recruitment by the BCL6 BTB Domain. Molecular Cell 12, 1551-1564 (2003).

McGregor CL, Chen L, Pomroy NC, Hwang P, Go S, Chakrabartty A and Privé GG. Lipopeptide Detergents Designed for the Structural Study of Membrane Proteins. Nature Biotechnology 2, 171-176 (2003).

Ahn VE, Faull KF, Whitelegge JP, Fluharty, AL and Privé, GG. Crystal structure of saposin B reveals a dimeric shell for lipid binding. PNAS 100: 38-43 (2003).

See all publication listings on PubMed.

Last Modified: 12 February 2009, 03:35 PM