Mechanistic basis for a molecular triage reaction

Abstract

Deciding a protein's fate Protein synthesis inside cells is finely balanced with protein degradation to maintain homeostasis. Shao et al. show how differential affinities and binding kinetics of three chaperones regulate the fate of tail-anchored (TA) membrane proteins. The chaperone SGTA binds to TA proteins and quickly transfers them to the targeting factor TRC40 through the C-terminal domain of the quality-control module BAG6. Proteins that dissociate from SGTA can either rebind or, at a slower rate, be bound by the C-terminal domain of BAG6. The latter puts them on a path to degradation. This hierarchy means that biosynthesis has the higher priority, but excess free TA proteins are degraded. Science , this issue p. 298