⚗️ biochemistry
Distal conformational steering by N-terminal pyroglutamylation enables subtype-selective GPCR activation across Aplysia PRXamide and human Neuromedin U signaling
This study reveals that N-terminal pyroglutamylation enables subtype-selective GPCR activation through a "distal steering" mechanism where the rigid modification reshapes the ligand's conformational ensemble to differentially engage receptor pockets without direct contact, a principle demonstrated across both Aplysia PRXamide and human Neuromedin U signaling systems.
Chang, J.-H., Liu, W.-J., Wu, S.-Q., Romanova, E., Liu, C., Liu, C., Pan, X., Li, F., Ding, X., Mao, R., Wang, H., Xu, J (…)2026-07-30