Generation of specific inhibitors of SUMO-1- and SUMO-2/3-mediated protein-protein interactions using Affimer (Adhiron) technology

We describe the use of the Affimer system of peptide display for the rapid isolation of synthetic binding proteins that inhibit SUMO-dependent protein-protein interactions mediated by SIMs both in vitro and in cells. Crucially, these synthetic proteins did not prevent SUMO conjugation either in vitro or in cell-based systems, enabling the specific analysis of SUMO-mediated protein-protein interactions. Furthermore, through structural analysis and molecular modeling, we explored the molecular mechanisms that may underlie their specificity in interfering with either SUMO-1–mediated interactions or interactions mediated by either SUMO-2 or SUMO-3. Not only will these reagents enable investigation of the biological roles of SUMOylation, but the Affimer technology used to generate these synthetic binding proteins could also be exploited to design or validate reagents or therapeutics that target other protein-protein interactions.

Source: Signal Transduction Knowledge Environment - November 14, 2017 Category: Science Authors: Hughes, D. J., Tiede, C., Penswick, N., Tang, A. A.-S., Trinh, C. H., Mandal, U., Zajac, K. Z., Gaule, T., Howell, G., Edwards, T. A., Duan, J., Feyfant, E., McPherson, M. J., Tomlinson, D. C., Whitehouse, A. Tags: STKE Research Resources Source Type: news