Determining receptor–ligand interaction of human galanin receptor type 3
2010 (English)In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 57, no 7, 804-811 p.Article in journal (Refereed) Published
Galanin is a neuropeptide found throughout the central and peripheral nervous systems of a wide range of species, ranging from human and mouse to frog and tuna. Galanin mediates its physiological roles through three receptors (GalR1–3), all members of the G-protein coupled receptor family. In mapping these roles, receptor subtype selective ligands are crucial tools. To facilitate the ligand design, data on receptor structure and interaction points are of great importance. The current study investigates the mechanism by which galanin interacts with GalR3. Mutated receptors were tested with competitive binding analysis in vitro. Our studies identify six mutagenic constructs that lost receptor affinity completely, despite being expressed at the cell surface. Mutations of the Tyr1033.33 in transmembrane helix (TM) III, His2516.51 in TM VI, Arg2737.35 or His2777.39 in TM VII, Phe2636.63 or Tyr2707.32 in the extracellular loop III all result in complete reduction of ligand binding. In addition, docking studies of an in silico model of GalR3 propose that four of the identified residues interact with pharmacophores situated within the galanin(2–6) sequence. This study provides novel insights into the interaction between ligands and GalR3 and highlights the requirement for correct design of targeting ligands.
Place, publisher, year, edition, pages
2010. Vol. 57, no 7, 804-811 p.
Galanin, Galanin receptor type 3, hGalR3, GPCR, Docking
Neurosciences Biochemistry and Molecular Biology
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-37226DOI: 10.1016/j.neuint.2010.08.018ISI: 000284437500013OAI: oai:DiVA.org:su-37226DiVA: diva2:295543
FunderSwedish Research CouncilEU, FP7, Seventh Framework Programme, 201924Knut and Alice Wallenberg Foundation