Jonathan V. Sweedler

Distal conformational steering by N-terminal pyroglutamylation enables subtype-selective GPCR activation across Aplysia PRXamide and human Neuromedin U signaling

A “PTM distal steering” mechanism is defined that bridges “lock-key” and “induced-fit” paradigms and establish a general principle by which a minimal, non-contacting modification encodes receptor preference through ligand conformational biasing and pocket-dependent permissiveness, providing a chemical framework for opt...