Structural insights into galanin receptor signaling

Abstract

SignificanceGalanin exerts various physiological functions through galanin receptors, including antinociceptive activity, depression, and sleep. Here, we reveal a distinct binding mode of galanin peptide in galanin receptors from that of the published structures of peptide-bound GPCRs. Moreover, our work shows that the neuromodulator zinc ion negatively modulates galanin signaling in the central nervous system and further advances our understanding of mechanisms of G protein selectivity of GPCRs. These structures will provide a framework for rational design of ligands targeting GALRs for potential therapeutic applications.