Research ResourceBiochemistry

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

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Sci. Signal.  14 Nov 2017:
Vol. 10, Issue 505, eaaj2005
DOI: 10.1126/scisignal.aaj2005

Artificial proteins target SUMO

SUMOylation is the covalent attachment of SUMO-1, SUMO-2, SUMO-3, or combinations thereof to target proteins to control protein function and localization. Hughes et al. screened a library of artificial proteins called Affimers to identify those that bound to SUMO-1 or SUMO-2 (which is nearly identical to SUMO-3) and incorporated a negative selection step to remove SUMO-2–binding Affimers that also bound to SUMO-1. The authors identified Affimers that recognized SUMO-1, SUMO-2 and SUMO-3 (SUMO-2/3), or all three isoforms. Biochemical and cellular assays showed that these SUMO-specific Affimers (S-Affs) did not interfere with SUMO conjugation or deconjugation but inhibited a cellular stress response that required SUMO-mediated protein-protein interactions. In addition to generating S-Affs that will be useful tools for studying SUMO-dependent cellular processes, this study also shows the applicability of this technology for generating reagents that interfere with specific protein-protein interactions for basic research and potentially for clinical development (see the Protocol by Tang et al.).