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

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)
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

Structural model of Pol II from the Cramer laboratory where bars' color and thickness represent interaction scores
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.
J Proteome Res. 2022 Apr 1;21(4):1073-1082. doi: 10.1021/acs.jproteome.1c00938
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.
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

A Network of Protein Complexes Involving the RNAP II Basal Transcription Machinery
Team

Asmae Moursli
PhD Student

Vijaya Madoo
Administrative Assistant

Dr. Maxime Pinard
Senior Associate Researcher
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Christian Poitras
System Analyst
Contact
Laboratoire de Benoit Coulombe
https://www.benoitcoulombe.ca/
Institut de recherches cliniques de Montréal (IRCM)
110 Avenue des Pins Ouest
Montréal, Québec, Canada
H2W 1R7
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