Recovering protein-protein and domain-domain interactions from aggregation of IP-MS proteomics of coregulator complexes.
Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/.
Department of Pharmacology and Systems Therapeutics, Systems Biology Center New York (SBCNY), Mount Sinai School of Medicine, New York, New York, United States of America.
Amin R
AR
Mazloom
Ruth
R
Dannenfelser
Neil R
NR
Clark
Arsen V
AV
Grigoryan
Kathryn M
KM
Linder
Timothy J
TJ
Cardozo
Julia C
JC
Bond
Aislyn D W
AD
Boran
Ravi
R
Iyengar
Anna
A
Malovannaya
Rainer B
RB
Lanz
Avi
A
Ma'ayan
D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D015233:Models, Statistical; D008968:Molecular Conformation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000737:chemistry; D054648:Protein Phosphatase 2 / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods*; D012984:Software; D000099317:Hippo Kinases
D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; C517191:PPP2R1A protein, human; C530660:STK25 protein, human; D000099317:Hippo Kinases