Functional role of the extracellular N-terminal domain of neuropeptide Y subfamily receptors in membrane integration and agonist-stimulated internalization.

摘要: The N terminus is the most variable element in G protein-coupled receptors (GPCRs), ranging from seven residues up to approximately 5900 residues. For family B and C GPCRs it described that at least part of ligand binding site located within terminus. Here we investigated role neuropeptide Y receptor family, which belongs class A GPCRs. We cloned differentially truncated mutants, was partially or completely deleted. found, eight amino acids are sufficient for full signal transduction activity. Interestingly, could show no specific but rather extension first transmembrane helix by any activity also membrane integration case hY(1) hY(4) receptors. In contrast, complete deletion hY(2) resulted a mutant fully integrated does not bind very well internalizes much slower compared wild type receptor. these effects be reverted N-terminal extension. Accordingly, important function termini seems stabilization ensure correct structure, obviously essential binding, into cell internalization.