| Title: | Evolution of synthetic signaling scaffolds by recombination of modular protein domains |
| Author(s): | Lai A; Sato PM; Peisajovich SG; |
| Address: | "Department of Cell and Systems Biology University of Toronto 25 Harbord Street, Toronto, Ontario M5S 3G5, Canada" |
| ISSN/ISBN: | 2161-5063 (Electronic) 2161-5063 (Linking) |
| Abstract: | "Signaling scaffolds are proteins that interact via modular domains with multiple partners, regulating signaling networks in space and time and providing an ideal platform from which to alter signaling functions. However, to better exploit scaffolds for signaling engineering, it is necessary to understand the full extent of their modularity. We used a directed evolution approach to identify, from a large library of randomly shuffled protein interaction domains, variants capable of rescuing the signaling defect of a yeast strain in which Ste5, the scaffold in the mating pathway, had been deleted. After a single round of selection, we identified multiple synthetic scaffold variants with diverse domain architectures, able to mediate mating pathway activation in a pheromone-dependent manner. The facility with which this signaling network accommodates changes in scaffold architecture suggests that the mating signaling complex does not possess a single, precisely defined geometry into which the scaffold has to fit. These relaxed geometric constraints may facilitate the evolution of signaling networks, as well as their engineering for applications in synthetic biology" |
| Keywords: | "Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism *Evolution, Molecular Mutagenesis, Site-Directed Pheromones/metabolism Protein Interaction Domains and Motifs Saccharomyces cerevisiae/genetics/growth & development/*metabolism Saccharomy;" |
| Notes: | "MedlineLai, Andicus Sato, Paloma M Peisajovich, Sergio G eng Research Support, Non-U.S. Gov't 2015/01/15 ACS Synth Biol. 2015 Jun 19; 4(6):714-22. doi: 10.1021/sb5003482. Epub 2015 Jan 20" |
