Abstract
The melanocortin-3 receptor (MC3R) is a G protein-coupled receptor involved in regulating energy metabolism, cardiovascular function, and inflammation. To gain a better understanding of the structure-function relationship of the MC3R, we used alaninescanning mutagenesis to investigate the functions of residues 247–273 in the third intracellular loop (ICL3) of the human MC3R (hMC3R). Ligand binding and signaling parameters of the mutants were measured. The results showed that six mutants at the N terminus of ICL3 had decreased receptor occupancy (an estimate of relative binding capacity) whereas six mutants at the C terminus of ICL3 had increased receptor occupancy. M247A, R252A, H254A, and K256A had decreased maximal responses (M247A also had increased EC50) whereas F250A, P262A, and H272A had increased maximal responses. None of the mutants was constitutively active. The binding and signaling properties of the other mutants were not significantly different from that of the wild type hMC3R. In summary, we presented detailed functional data on the functions of the residues in ICL3 of hMC3R, providing important constraints for modeling ligand binding and G protein coupling/activation in the hMC3R.
Keywords: Melanocortin-3 receptor, alanine scanning mutagenesis, binding, signaling.
Current Pharmaceutical Design
Title:Functions of the Third Intracellular Loop of the Human Melanocortin-3 Receptor
Volume: 19 Issue: 27
Author(s): Zhi-Qiang Wang and Ya-Xiong Tao
Affiliation:
Keywords: Melanocortin-3 receptor, alanine scanning mutagenesis, binding, signaling.
Abstract: The melanocortin-3 receptor (MC3R) is a G protein-coupled receptor involved in regulating energy metabolism, cardiovascular function, and inflammation. To gain a better understanding of the structure-function relationship of the MC3R, we used alaninescanning mutagenesis to investigate the functions of residues 247–273 in the third intracellular loop (ICL3) of the human MC3R (hMC3R). Ligand binding and signaling parameters of the mutants were measured. The results showed that six mutants at the N terminus of ICL3 had decreased receptor occupancy (an estimate of relative binding capacity) whereas six mutants at the C terminus of ICL3 had increased receptor occupancy. M247A, R252A, H254A, and K256A had decreased maximal responses (M247A also had increased EC50) whereas F250A, P262A, and H272A had increased maximal responses. None of the mutants was constitutively active. The binding and signaling properties of the other mutants were not significantly different from that of the wild type hMC3R. In summary, we presented detailed functional data on the functions of the residues in ICL3 of hMC3R, providing important constraints for modeling ligand binding and G protein coupling/activation in the hMC3R.
Export Options
About this article
Cite this article as:
Wang Zhi-Qiang and Tao Ya-Xiong, Functions of the Third Intracellular Loop of the Human Melanocortin-3 Receptor, Current Pharmaceutical Design 2013; 19 (27) . https://dx.doi.org/10.2174/1381612811319270005
DOI https://dx.doi.org/10.2174/1381612811319270005 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Tendon Regeneration and Repair with Adipose Derived Stem Cells
Current Stem Cell Research & Therapy Mixed Connective Tissue Disease (MCTD) – A Coming of Age
Current Rheumatology Reviews Iron Chelators in Cancer Chemotherapy
Current Topics in Medicinal Chemistry The Paths to Neurodegeneration in Genetic Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Estrogen Receptor-α: Plasma Membrane Localization and Functions
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Albumin Infusion Therapy in Stroke, Sepsis and the Critically Ill
Current Nutrition & Food Science Impact of Sphingolipid Mediators on the Determination of Cochlear Survival in Ototoxicity
Current Molecular Pharmacology The Heme Oxygenase/Biliverdin Reductase Pathway in Drug Research and Development
Current Drug Metabolism Efficient Synthesis of 6-O-methyl-scutellarein from Scutellarin via Selective Methylation
Letters in Organic Chemistry NF-κB as a Therapeutic Target for Transcription Factor Decoy Strategy in Inflammatory Diseases
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Chemical Biology of Immunophilin Ligands
Current Medicinal Chemistry Protective Effects of Anesthetics on the Spinal Cord
Current Pharmaceutical Design Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach
Current Drug Targets Targeting Transient Receptor Potential Canonical Channels for Diseases of the Nervous System
Current Drug Targets Post Cardiovascular Surgery Atrial Fibrillation. Biomarkers Determining Prognosis
Current Medicinal Chemistry Pulmonary Hypertension: Clinical Presentation, Diagnosis, Treatment,and Dana Point World Symposium Highlights
Current Respiratory Medicine Reviews Diagnostic Value of HLA Typing in Pathogenesis of Cardiomyopathy
Cardiovascular & Hematological Disorders-Drug Targets Erythropoietin Treatment in Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Current Drug Delivery Compounds that Combine Aldose Reductase Inhibitory Activity and Ability to Prevent the Glycation (Glucation and/or Fructation) of Proteins as Putative Pharmacotherapeutic Agents
Drug Design Reviews - Online (Discontinued) Technetium-99m Cysteine; A Novel Radiopharmaceutical for Detection of Experimental Myocardial Infarction in Rats
Current Radiopharmaceuticals