Ligand binding neuropeptide receptors

Beck-Siddnger AG, Wieland HA, Wittenben H, Willim KD, Rudolf K, et al. 1994. Complete L-alanine scan of neuropeptide Y reveals ligands binding to Y1 and Y2 receptors with distinguished conformations. Eur J Biochem 225 947. 

Naldini, L., D. Cirillo, T. W. Moody, P. M. Comoglio, J. Schlessinger and R. Kris (1990). Solubilization of the receptor for the neuropeptide gastrin-releasing peptide (bombesin) with functional ligand binding properties. Biochemistry 29(21) 5153— 5160. 

Grundemar, L., Kahl, U., Langel, U., Callreus, T. Bienen, Beyermann, M. (1996) Ligand binding and functional effects of systematic double D-amino-acid residue substituted neuropeptide Y analogs on Y1 and Y2 receptors Regul. Peptides 62, 131-136. 

Kahl, U., Langel, U., Bartfai, T. Grundemar, L. (1994) Functional effects and ligand binding of chimeric galanin-neuropeptide Y (NPY) peptides on NPY and galanin receptor types. Br. J. Pharmacol. Ill, 1129-1134. 

Mihara, S.-I., Shigeri, Y. Fujimoto, M. (1990) Neuropeptide Y receptor in cultured vascular smooth muscle cells ligand binding and increase in cytosolic free Ca2+. Biochem. Int. 22, 205-212. 

Sautel, M., Martinez, R., Munoz, M., Peitsch, M.C., Beck-Sickinger, A.G. Walker, P. (1995) Role of a hydrophobic pocket of the human Y1 neuropeptide Y receptor in ligand binding. Mol. Cell. Endocrinol. 112, 215-222. 

The ion channel receptors are similar in structure to the nicotinic acetylcholine receptor (see Fig. 11.3). Signal transduction consists of the conformational change when ligand binds. Most small molecule neurotransmitters and some neuropeptides use ion channel receptors. 

This review siunmarizes approaches based on multiple peptide synthesis for the determination of structural and conformational requirements of peptide hormones for binding at and activation of their specific receptors. These include various systematic scans, several methods to stabihze distinct local conformations as well as secondary or even tertiary structures. Examples of their application are mainly taken from various midti-hgand/multi-receptor systems including that of the neuropeptide Y (NPY) family. Moreover, basic ligand-receptor binding assays and functional cell-based in vitro assays, which are used to investigate the interaction of native and modified peptide ligands with their receptors, are briefly reviewed. 

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