Distal conformational steering by N-terminal pyroglutamylation enables subtype-selective GPCR activation across Aplysia PRXamide and human Neuromedin U signaling
Jian Hui Chang, Wei-Jia Liu, Shao-Qian Wu, Elena V. Romanova, Chengyi Liu, Cuiping Liu, Xing Pan, Fan Li, Xueying Ding, Ruiting Mao, Huiying Wang, Juping Xu, Ping Fu, Yi-Long Zhang, Qingchun Jin, , Jian Jing
The paper shows how N-terminal pyroglutamylation (pQ) biases GPCR activation by altering ligand conformation and receptor pocket mechanics, enabling subtype-selective signaling in both Aplysia and human systems.
bioRxiv · Jul 30, 2026 · PreprintBiochemistry