Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair.

ABSTRACT: Signaling pathways depend on regulatory protein-protein interactions; controlling these interactions in cells has important applications for reengineering biological functions. As many regulatory proteins are modular, considerable progress in engineering signaling circuits has been made by recombining commonly occurring domains. Our ability to predictably engineer cellular functions, however, is constrained by complex crosstalk observed in naturally occurring domains. Here we demonstrate a strategy for improving and simplifying protein network engineering: using computational design to create orthogonal (non-crossreacting) protein-protein interfaces. We validated the design of the interface between a key signaling protein, the GTPase Cdc42, and its activator, Intersectin, biochemically and

SUBMITTER: Kapp GT 

PROVIDER: S-EPMC3325720 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature