Exploring the Universe of Protein-Protein Interactions

Discovery of the PAQosome

Our Technology Platforms
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Affinity Purification coupled with Mass Spectrometry (AP-MS)
Purification and characterization of soluble protein complexes
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Proximity-dependent labeling coupled with Mass spectrometry (BioID-MS)
Characterization of insoluble protein complexes
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Mass Spectrometry Immuno Affinity (MSIA)
Targeted protein quantification
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FAB-Phage Display screening (PhD)
Unbiased discovery of FAB-phages recognizing specific cell epitopes
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Quantitative Single-Cell Proteomics (SCP)
Identification of proteins at single-cell resolution
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Small-molecule screening (SMS)
Discovery of small molecules affecting biological/biochemical functions
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Artificial Intelligence-Alphafold2 multimer-Binary (AI-AF2m-Binary)
Determination of pairwise protein-protein interactions in the AlphaFold database
MOST RECENT ARTICLE
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
FEATURED ARTICLES
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

Dr. Esen Sokullu
Post Doctoral Fellow

Christian Poitras
System Analyst

Dr. Maxime Pinard
Senior Associate Researcher

Asmae Moursli
PhD Student

Vijaya Madoo
Administrative Assistant
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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