Abstract
Receptor activity-modifying proteins (RAMPs) 1–3, which are classified as type I transmembrane proteins, serve as the partner proteins of several family B GPCRs for physiologically active peptides, including the calcitonin receptor- like receptor (CLR). The properties of the GPCRs are defined by the RAMP and peptide ligand combination. The CLR•RAMP1 heterodimer functions mainly as the calcitonin gene-related peptide (CGRP) receptor, while the CLR•RAMP2 and CLR•RAMP3 heterodimers primarily function as the adrenomedullin 1 and adrenomedullin 2 (AM1 and AM2) receptors, respectively. The crystal structures of the RAMP1 and RAMP2 ectodomains exhibited three-helix bundles, and those of their complexes with the N-terminal extracellular domain of CLR revealed how the two ectodomains associate to form the CGRP and AM1 receptors, respectively. On this structural framework, the various intermolecular interactions of CLR with RAMP1 and RAMP2 result in the distinct shapes of the putative ligand-binding sites, where several residues are uniquely presented. Therefore, the differences in the shapes and the presented residues of the binding sites determine the specificities of the receptors to either CGRP or AM. These structural features of the ectodomains are consistent with mutagenesis results, and are useful to further examine the binding modes of the peptide ligands to the full-length CGRP and AM1 receptors.
Keywords: Receptor activity-modifying protein, calcitonin receptor-like receptor, adrenomedullin, calcitonin gene-related peptide, neovascularization, migraine, antagonist, crystal structure.
Current Protein & Peptide Science
Title:Ectodomain Structures of the CGRP and AM Receptors
Volume: 14 Issue: 5
Author(s): Seisuke Kusano and Shigeyuki Yokoyama
Affiliation:
Keywords: Receptor activity-modifying protein, calcitonin receptor-like receptor, adrenomedullin, calcitonin gene-related peptide, neovascularization, migraine, antagonist, crystal structure.
Abstract: Receptor activity-modifying proteins (RAMPs) 1–3, which are classified as type I transmembrane proteins, serve as the partner proteins of several family B GPCRs for physiologically active peptides, including the calcitonin receptor- like receptor (CLR). The properties of the GPCRs are defined by the RAMP and peptide ligand combination. The CLR•RAMP1 heterodimer functions mainly as the calcitonin gene-related peptide (CGRP) receptor, while the CLR•RAMP2 and CLR•RAMP3 heterodimers primarily function as the adrenomedullin 1 and adrenomedullin 2 (AM1 and AM2) receptors, respectively. The crystal structures of the RAMP1 and RAMP2 ectodomains exhibited three-helix bundles, and those of their complexes with the N-terminal extracellular domain of CLR revealed how the two ectodomains associate to form the CGRP and AM1 receptors, respectively. On this structural framework, the various intermolecular interactions of CLR with RAMP1 and RAMP2 result in the distinct shapes of the putative ligand-binding sites, where several residues are uniquely presented. Therefore, the differences in the shapes and the presented residues of the binding sites determine the specificities of the receptors to either CGRP or AM. These structural features of the ectodomains are consistent with mutagenesis results, and are useful to further examine the binding modes of the peptide ligands to the full-length CGRP and AM1 receptors.
Export Options
About this article
Cite this article as:
Kusano Seisuke and Yokoyama Shigeyuki, Ectodomain Structures of the CGRP and AM Receptors, Current Protein & Peptide Science 2013; 14 (5) . https://dx.doi.org/10.2174/13892037113149990054
DOI https://dx.doi.org/10.2174/13892037113149990054 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Platelet Glycoprotein IIb / IIIa Inhibition and its Clinical Use
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Non-Steroidal LXR Agonists; An Emerging Therapeutic Strategy for the Treatment of Atherosclerosis
Recent Patents on Cardiovascular Drug Discovery Structure and Thermodynamics of Drug-RNA Aptamer Interactions
Mini-Reviews in Medicinal Chemistry Editorial [Hot Topic:Positron Emission Tomography (PET) in Medicinal Chemistry and Drug Discovery (Guest Editor: Ming-Rong Zhang)]
Current Topics in Medicinal Chemistry Protein/ Hormone Based Nanoparticles as Carriers for Drugs Targeting Protein-Protein Interactions
Current Topics in Medicinal Chemistry Pharmacogenetics and Pharmagenomics, Trends in Normal and Pathological Aging Studies: Focus on p53
Current Pharmaceutical Design Nanoparticle-Based Combination Therapy for Cancer Treatment
Current Pharmaceutical Design Recent Developments in Cardiovascular Drug Therapy: Treatment of Atrial Arrhythmias with New Class III Drugs and beyond
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Renal Solute Transporters and Their Relevance to Serum Urate Disorder
Current Hypertension Reviews The Chemistry and Pharmacology of Tetrahydropyridines
Current Medicinal Chemistry The Sigma Receptor: Evolution of the Concept in Neuropsychopharmacology
Current Neuropharmacology Therapeutic Relevance of the Allosteric Modulation of the 5-HT Transporter
Current Signal Transduction Therapy Potential Therapeutic Effects of Physical Exercise for Bipolar Disorder
CNS & Neurological Disorders - Drug Targets Preparation and Optimization of Fast Dissolving Film of Naratriptan Hydrochloride
Recent Patents on Drug Delivery & Formulation Meet the Editorial Board:
CNS & Neurological Disorders - Drug Targets Major Mental Disorders and Violence: A Critical Update
Current Psychiatry Reviews Does the MK2-dependent Production of TNFα Regulate mGluR-dependent Synaptic Plasticity?
Current Neuropharmacology Theoretical Approaches to Protein Aggregation
Protein & Peptide Letters subject Index To Volume 2
Current Molecular Medicine Metabotropic Glutamate Receptors Modulate Periaqueductal Grey Descending Analgesic System
Central Nervous System Agents in Medicinal Chemistry