Translational Proteomics lab

Director, Benoit Coulombe PhD

Mission

OUR GROUP IS USING AI TO IDENTIFY PROTEIN-PROTEIN INTERACTIONS BETWEEN HIGH PANDEMIC RISK ZOONOTIC RESPIRATORY VIRUSES AND HOST CELLS FOR ANTIVIRAL DRUG DISCOVERY

AlphaFold-pairs

AlphaFold-pairs is an algorithm that uses the AI system AlphaFold-Multimer (DeepMind/Google) to identify direct physical protein-protein interactions of human or viral origin. AlphaFold-pairs has been developed by the Translational Proteomics lab at the Montreal Clinical Research Institute

Interaction between HA of G4 virus and HSP90B1 as found by AlphaFold

Green and Blue : HA protein from G4 virus

Orange and Yellow: Human HSP90B1

Blue : Residues of HA that are part of the interface with HSP90B1

Yellow : Residues of HSP90B1 that are part of the interface with HA

AlphaFold-pairs score of 33 while the average for other HA proteins is 6

Upcoming Presentations by Benoit Coulombe

June 10-12 2024, Molecular chaperones in cancer, CNIO Stop Cancer, Madrid, Spain (Invited)

Recent

Most Recent Article

AI predicts protein direct physical interactions with AlphaFold-pairs

Poitras C, Lamontage F, Grandvaux N, Song H, Pinard M, Coulombe B.

High-accuracy mapping of human and viral direct physical protein-protein interactions using the novel computational system AlphaFold-pairs

IN PRESS

Protein-Protein interactions in human POLR2

Structural model of Pol II from the Cramer laboratory where bars' color and thickness represent interaction scores

Featured

Featured Articles

A mouse model to study RNA polymerase III-related leukodystrophies

Michell-Robinson M, Watt KEN, Grouza V, Macintosh J, Pinard M, Tuznik M, Chen X, Darbelli L, Wu CL, Perrier S, Chitsaz D, Uccelli NA, Liu H, Cox TC, Müller C, Kennedy TE, Coulombe B, Rudko D, Trainor PA, Bernard G.

Hypomyelination, hypodontia and craniofacial abnormalities in a Polr3b mouse model of leukodystrophy

IN PRESS

Discovery of a drug that stimulates protein complex assembly

Pinard M, Dastpeyman S, Poitras C, Bernard G, Gauthier MS, Coulombe B.

Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H

Mol Brain. 2022 Nov 30;15(1):98. doi: 10.1186/s13041-022-00974-z.

Schematic representation of Pol III assembly defects caused by various mutated subunits

Discovery of a novel mode of substrate selection by the PAQosome

Pinard M, Cloutier P, Poitras C, Gauthier MS, Coulombe B.

Unphosphorylated Form of the PAQosome Core Subunit RPAP3 Binds Ribosomal Preassembly Complexes to Modulate Ribosome Biogenesis

J Proteome Res. 2022 Apr 1;21(4):1073-1082. doi: 10.1021/acs.jproteome.1c00938

PAQosome Subunit RPAP3 Binds Ribosomal Preassembly Complexes

Discovery of a novel neurodegenerative disorder and causative mutations

Djordjevic D, Pinard M, Gauthier MS, Smith-Hicks C, Hoffman TL, Wolf NI, Oegema R, van Binsbergen E, Baskin B, Bernard G, Fribourg S, Coulombe B, Yoon G.

De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy

Am J Hum Genet. 2021 Jan 7;108(1):186-193. doi: 10.1016/j.ajhg.2020.12.002

Model of POLR3 in transcription initiation state

A mechanistic model for interactome biogenesis

Coulombe B, Cloutier P, Gauthier MS.

How do our cells build their protein interactome?

Nat Commun. 2018 Jul 27;9(1):2955. doi: 10.1038/s41467-018-05448-2.

Representation of putative alternative PAQosomes

Summary of the PAQosome structure and function

Houry WA, Bertrand E, Coulombe B.

The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation

Trends Biochem Sci. 2018 Jan;43(1):4-9. doi: 10.1016/j.tibs.2017.11.001.

Schematic of the PAQosome Structure, Adaptors, and Clients

Discovery of leukodystrophy-causing mutations that target assembly of RNA pol III

Thiffault I, Wolf NI, Forget D, Guerrero K, Tran LT, Choquet K, Lavallée-Adam M, Poitras C, Brais B, Yoon G, Sztriha L, Webster RI, Timmann D, van de Warrenburg BP, Seeger J, Zimmermann A, Máté A, Goizet C, Fung E, van der Knaap MS, Fribourg S, Vanderver A, Simons C, Taft RJ, Yates JR 3rd, Coulombe B, Bernard G.

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

Nat Commun. 2015 Jul 7;6:7623. doi: 10.1038/ncomms8623.

Impact of POLR1C mutations on polymerase assembly and nuclear import

Discovery of molecular adaptors for substrate selection by the PAQosome

Cloutier P, Poitras C, Durand M, Hekmat O, Fiola-Masson É, Bouchard A, Faubert D, Chabot B, Coulombe B.

R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein

Nat Commun. 2017 May 31;8:15615. doi: 10.1038/ncomms15615.

R2TP substrates

Using machine learning to build protein interaction networks

Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Thérien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B.

Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme

Mol Cell. 2007 Jul 20;27(2):262-274. doi: 10.1016/j.molcel.2007.06.027.

Application of machine learning to construct an interaction network for the human RNA polymerase II transcription machinery, leading to discovery of the 7SK capping enzyme