Differential contributions of motilin receptor extracellular domains for peptide and non-peptidyl agonist binding and activity

The Journal of Biological Chemistry
Bunzo MatsuuraMorikazu Onji

Abstract

The family of G protein-coupled receptors that includes receptors for motilin, ghrelin, and growth hormone secretagogue has substantial potential importance as drug targets. Understanding of the molecular basis of hormone binding and receptor activation should provide insights that are helpful in the development of such drugs. We previously examined the unique second extracellular loop domain of the motilin receptor, identifying key epitopes in perimembranous locations at each end of this long loop (Matsuura, B., Dong, M., and Miller, L. J. (2002) J. Biol. Chem. 277, 9834-9839). Here, we have extended that work, examining the other predicted extracellular domains of the motilin receptor by using sequential deletions of segments ranging from one to six amino acid residues and site-directed alanine replacement mutagenesis approaches. Each construct was transiently expressed in COS cells, and characterized for motilin- and erythromycin-stimulated intracellular calcium responses and motilin radioligand binding. Only those receptor segments that included key Cys residues in positions 25, 30, and 111 or perimembranous regions at the ends of the amino terminus and the first and third extracellular loops disrupted motilin biological ac...Continue Reading

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Citations

Mar 1, 2008·Nature Reviews. Drug Discovery·Gareth J Sanger, Kevin Lee
May 17, 2008·The Journal of Biological Chemistry·Irina VetterPeter J Cabot
Apr 3, 2012·Regulatory Peptides·Hiroaki NunoiMorikazu Onji
Apr 14, 2009·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Hiroyuki KaiyaKenji Kangawa
Aug 4, 2012·Current Opinion in Pharmacology·Gareth J Sanger
Apr 25, 2008·General and Comparative Endocrinology·Ichiro YamamotoMinoru Tanaka
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Feb 13, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Jan 11, 2008·Current Opinion in Endocrinology, Diabetes, and Obesity·Pierre Poitras, Theo L Peeters
Jan 25, 2019·Nature Reviews. Endocrinology·Eveline DelooseJan Tack
Nov 23, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hitoo TokunagaMorikazu Onji
Apr 3, 2019·International Journal of Molecular Sciences·Tomoe KawamuraYoichi Hiasa
Jul 1, 2020·JCI Insight·Tomoki MaekawaGeorge Hajishengallis

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