Structural Complexity and Plasticity of Signaling Regulation at the Melanocortin-4 Receptor

Differential Signaling Profiles of MC4R Mutations with Three Different Ligands

(2020) Sarah Paisdzior et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Structural basis of ligand recognition and self-activation of orphan GPR52

(2020) Xi Lin et al.   NATURE

Impact of GPCR Structures on Drug Discovery

(2020) Miles Congreve et al.   CELL

Drug Therapy in Obesity: A Review of Current and Emerging Treatments

(2020) David M. Williams et al.   Diabetes Therapy

Molecular chaperones and G protein-coupled receptor maturation and pharmacology

(2020) Ya-Xiong Tao   MOLECULAR AND CELLULAR ENDOCRINOLOGY

Biased signaling in fish melanocortin-4 receptors (MC4Rs): Divergent pharmacology of four ligands on spotted scat (Scatophagus argus) and grass carp (Ctenopharyngodon idella) MC4Rs

(2020) Zhao Yang et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

Crystal Structure of the Human Cannabinoid Receptor CB2

(2019) Xiaoting Li et al.   CELL

An online resource for GPCR structure determination and analysis

(2019) Christian Munk et al.   NATURE METHODS

Melanocortin-4 Receptor Signalling: Importance for Weight Regulation and Obesity Treatment

(2019) Peter Kühnen et al.   TRENDS IN MOLECULAR MEDICINE

Diverse GPCRs exhibit conserved water networks for stabilization and activation

(2019) A. J. Venkatakrishnan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity

(2019) Luca A. Lotta et al.   CELL

Distinct Dopamine D2 Receptor Antagonists Differentially Impact D2 Receptor Oligomerization

(2019) Elise Wouters et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Current Mechanistic and Pharmacodynamic Understanding of Melanocortin-4 Receptor Activation

(2019) Sharma et al.   MOLECULES

Illuminating G-Protein-Coupling Selectivity of GPCRs

(2019) Asuka Inoue et al.   CELL

Computational prediction of GPCR oligomerization

(2019) Andrea Townsend-Nicholson et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Serotonin receptor oligomerization regulates cAMP-based signaling

(2019) Sonal Prasad et al.   JOURNAL OF CELL SCIENCE

Signal Transduction and Pathogenic Modifications at the Melanocortin-4 Receptor: A Structural Perspective

(2019) Nicolas Heyder et al.   Frontiers in Endocrinology

Bremelanotide: First Approval

(2019) Sohita Dhillon et al.   DRUGS

Obesity‐associated mutant MC4 receptors with normal Gα s coupling frequently exhibit other discoverable pharmacological and biochemical defects

(2019) Taneisha Gillyard et al.   JOURNAL OF NEUROENDOCRINOLOGY

Harnessing Ion-Binding Sites for GPCR Pharmacology

(2019) Barbara Zarzycka et al.   PHARMACOLOGICAL REVIEWS

Oligomeric Receptor Complexes and Their Allosteric Receptor-Receptor Interactions in the Plasma Membrane Represent a New Biological Principle for Integration of Signals in the CNS

(2019) Dasiel O. Borroto-Escuela et al.   Frontiers in Molecular Neuroscience

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein‐coupled receptors

(2019) Stephen P H Alexander et al.   BRITISH JOURNAL OF PHARMACOLOGY

Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder

(2019) James A. Simon et al.   OBSTETRICS AND GYNECOLOGY

Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology

(2019) Kai-Qiang Zhang et al.   Frontiers in Endocrinology

Orange-spotted grouper melanocortin-4 receptor: Modulation of signaling by MRAP2

(2019) Ying-Zhu Rao et al.   GENERAL AND COMPARATIVE ENDOCRINOLOGY

The constitutive activity of melanocortin‐4 receptors in cAMP pathway is allosterically modulated by zinc and copper ions

(2019) Reet Link et al.   JOURNAL OF NEUROCHEMISTRY

The Molecular Basis of G Protein–Coupled Receptor Activation

(2018) William I. Weis et al.   Annual Review of Biochemistry

Pathophysiology of melanocortin receptors and their accessory proteins

(2018) T.V. Novoselova et al.   BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM

Sodium functions as a negative allosteric modulator of the oxytocin receptor

(2018) Andrea Schiffmann et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Recent advances in the determination of G protein-coupled receptor structures

(2018) David M Thal et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Prediction and Targeting of Interaction Interfaces in G-protein Coupled Receptor Oligomers

(2018) Anke C. Schiedel et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Developing a Biased Unmatched Bivalent Ligand (BUmBL) Design Strategy to Target the GPCR Homodimer Allosteric Signaling (cAMP over β-Arrestin 2 Recruitment) Within the Melanocortin Receptors

(2018) Cody J. Lensing et al.   JOURNAL OF MEDICINAL CHEMISTRY

MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency

(2018) Karine Clément et al.   NATURE MEDICINE

Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling

(2018) Kate L. White et al.   STRUCTURE

Intracellular Transfer of Na + in an Active-State G-Protein-Coupled Receptor

(2018) Owen N. Vickery et al.   STRUCTURE

GPCRs and Signal Transducers: Interaction Stoichiometry

(2018) Vsevolod V. Gurevich et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

MC4R Agonists: Structural Overview on Antiobesity Therapeutics

(2018) Juliana Pereira Lopes Gonçalves et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Mechanistic insights into allosteric regulation of the A2A adenosine G protein-coupled receptor by physiological cations

(2018) Libin Ye et al.   Nature Communications

The sphingosine 1-phosphate receptor 2 is shed in exosomes from breast cancer cells and is N-terminally processed to a short constitutively active form that promotes extracellular signal regulated kinase activation and DNA synthesis in fibroblasts

(2018) Ashref El Buri et al.   Oncotarget

Binding, Thermodynamics, and Selectivity of a Non-peptide Antagonist to the Melanocortin-4 Receptor

(2018) Noureldin Saleh et al.   Frontiers in Pharmacology

Melanocortin Receptor 4 Signaling Regulates Vertebrate Limb Regeneration

(2018) Mengshi Zhang et al.   DEVELOPMENTAL CELL

Melanocortin-4 receptor in swamp eel ( Monopterus albus ): Cloning, tissue distribution, and pharmacology

(2018) Ti-Lin Yi et al.   GENE

Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor

(2018) Yi-Lynn Liang et al.   NATURE

Allosteric Na+-binding site modulates CXCR4 activation

(2018) Xiaojing Cong et al.   PHYSICAL CHEMISTRY CHEMICAL PHYSICS

GPCR homo-oligomerization

(2018) Graeme Milligan et al.   CURRENT OPINION IN CELL BIOLOGY

The interaction of MC3R and MC4R with MRAP2, ACTH, α-MSH and AgRP in chickens

(2017) Jiannan Zhang et al.   JOURNAL OF ENDOCRINOLOGY

Understanding the common themes and diverse roles of the second extracellular loop (ECL2) of the GPCR super-family

(2017) Michael J. Woolley et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

MC4R-dependent suppression of appetite by bone-derived lipocalin 2

(2017) Ioanna Mosialou et al.   NATURE

Trends in GPCR drug discovery: new agents, targets and indications

(2017) Alexander S. Hauser et al.   NATURE REVIEWS DRUG DISCOVERY

Melanocortin 4 receptor constitutive activity inhibits L-type voltage-gated calcium channels in neurons

(2017) F. Agosti et al.   NEUROSCIENCE

Extending the Structural View of Class B GPCRs

(2017) Chris de Graaf et al.   TRENDS IN BIOCHEMICAL SCIENCES

MRAP2 regulates ghrelin receptor signaling and hunger sensing

(2017) Dollada Srisai et al.   Nature Communications

Loss of the melanocortin-4 receptor in mice causes dilated cardiomyopathy

(2017) Michael J Litt et al.   eLife

Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency

(2017) Tinh-Hai Collet et al.   Molecular Metabolism

Single-molecule imaging reveals dimerization/oligomerization of CXCR4 on plasma membrane closely related to its function

(2017) Baosheng Ge et al.   Scientific Reports

Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, a 250-Fold Selective Melanocortin-4 Receptor (MC4R) Antagonist over the Melanocortin-3 Receptor (MC3R), Affects Energy Homeostasis in Male and Female Mice Differently

(2016) Cody J. Lensing et al.   ACS Chemical Neuroscience

Receptor activity-modifying proteins; multifunctional G protein-coupled receptor accessory proteins

(2016) Debbie L. Hay et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Biased signaling initiated by agouti-related peptide through human melanocortin-3 and -4 receptors

(2016) Zhao Yang et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Design of cyclized selective melanotropins

(2016) Minying Cai et al.   BIOPOLYMERS

Crystal Structure of the Human Cannabinoid Receptor CB 1

(2016) Tian Hua et al.   CELL

The expanding repertoire of receptor activity modifying protein (RAMP) function

(2016) Klara R. Klein et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

Molecular cloning, tissue distribution, and pharmacological characterization of melanocortin-4 receptor in spotted scat, Scatophagus argus

(2016) Jian-Tao Li et al.   GENERAL AND COMPARATIVE ENDOCRINOLOGY

Endogenous N-terminal Domain Cleavage Modulates α1D-Adrenergic Receptor Pharmacodynamics

(2016) Timothy S. Kountz et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Design and Characterization of Superpotent Bivalent Ligands Targeting Oxytocin Receptor Dimers via a Channel-Like Structure

(2016) Marta Busnelli et al.   JOURNAL OF MEDICINAL CHEMISTRY

An in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers

(2016) Cody J. Lensing et al.   JOURNAL OF MEDICINAL CHEMISTRY

60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH

(2016) Erica J P Anderson et al.   JOURNAL OF MOLECULAR ENDOCRINOLOGY

Upregulation of hepatic melanocortin 4 receptor during rat liver regeneration

(2016) Min Xu et al.   JOURNAL OF SURGICAL RESEARCH

Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region

(2016) A. J. Venkatakrishnan et al.   NATURE

Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist

(2016) Peter Kühnen et al.   NEW ENGLAND JOURNAL OF MEDICINE

Decreased melanocortin-4 receptor function conferred by an infrequent variant at the human melanocortin receptor accessory protein 2 gene

(2016) Laura Schonnop et al.   Obesity

What are they waiting for?—Tethered agonism in G protein-coupled receptors

(2016) Torsten Schöneberg et al.   PHARMACOLOGICAL RESEARCH

The complex binding mode of the peptide hormone H2 relaxin to its receptor RXFP1

(2016) Ashish Sethi et al.   Nature Communications

The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1

(2016) Anna L Chaly et al.   eLife

Insights into Basal Signaling Regulation, Oligomerization, and Structural Organization of the Human G-Protein Coupled Receptor 83

(2016) Anne Müller et al.   PLoS One

Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1

(2015) Jill E. Chrencik et al.   CELL

The Activation Mechanism of Glycoprotein Hormone Receptors with Implications in the Cause and Therapy of Endocrine Diseases

(2015) Antje Brüser et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, Increases Resting Energy Expenditure in Obese Individuals

(2015) Kong Y. Chen et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons

(2015) Masoud Ghamari-Langroudi et al.   NATURE

Native SAD is maturing

(2015) John P. Rose et al.   IUCrJ

Synthesis and evaluation of bivalent ligands for binding to the human melanocortin-4 receptor

(2014) Steve M. Fernandes et al.   BIOORGANIC & MEDICINAL CHEMISTRY

The Melanocortin-4 Receptor Is Expressed in Enteroendocrine L Cells and Regulates the Release of Peptide YY and Glucagon-like Peptide 1 In Vivo

(2014) Brandon L. Panaro et al.   Cell Metabolism

Chaperoning G Protein-Coupled Receptors: From Cell Biology to Therapeutics

(2014) Ya-Xiong Tao et al.   ENDOCRINE REVIEWS

The Evolution of the GPCR Signaling System in Eukaryotes: Modularity, Conservation, and the Transition to Metazoan Multicellularity

(2014) Alex de Mendoza et al.   Genome Biology and Evolution

Defect in MAPK Signaling As a Cause for Monogenic Obesity Caused By Inactivating Mutations in the Melanocortin-4 Receptor Gene

(2014) Shan He et al.   International Journal of Biological Sciences

Structure of the human P2Y12 receptor in complex with an antithrombotic drug

(2014) Kaihua Zhang et al.   NATURE

Allosteric sodium in class A GPCR signaling

(2014) Vsevolod Katritch et al.   TRENDS IN BIOCHEMICAL SCIENCES

Crystal structure of a common GPCR-binding interface for G protein and arrestin

(2014) Michal Szczepek et al.   Nature Communications

A Tethered Agonist within the Ectodomain Activates the Adhesion G Protein-Coupled Receptors GPR126 and GPR133

(2014) Ines Liebscher et al.   Cell Reports

Activation of MAPK by inverse agonists in six naturally occurring constitutively active mutant human melanocortin-4 receptors

(2013) Xiu-Lei Mo et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options

(2013) L Fani et al.   INTERNATIONAL JOURNAL OF OBESITY

Novel Structural and Functional Insights into M3Muscarinic Receptor Dimer/Oligomer Formation

(2013) Jianxin Hu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

hMRAPa increases αMSH-induced hMC1R and hMC3R functional coupling and hMC4R constitutive activity

(2013) Emma I Kay et al.   JOURNAL OF MOLECULAR ENDOCRINOLOGY

hMRAPa specifically alters hMC4R molecular mass and N-linked complex glycosylation in HEK293 cells

(2013) Emma I Kay et al.   JOURNAL OF MOLECULAR ENDOCRINOLOGY

Inhibition of melanocortin-4 receptor dimerization by substitutions in intracellular loop 2

(2013) Carolin L Piechowski et al.   JOURNAL OF MOLECULAR ENDOCRINOLOGY

Crystal structure of oligomeric β1-adrenergic G protein–coupled receptors in ligand-free basal state

(2013) Jianyun Huang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

The melanocortin 4 receptor: Oligomer formation, interaction sites and functional significance

(2012) Kathryn L. Chapman et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Human cytomegalovirus-encoded UL33 and UL78 heteromerize with host CCR5 and CXCR4 impairing their HIV coreceptor activity

(2012) K. Tadagaki et al.   BLOOD

Lifting the lid on GPCRs: the role of extracellular loops

(2012) M Wheatley et al.   BRITISH JOURNAL OF PHARMACOLOGY

Chronic Treatment With a Melanocortin-4 Receptor Agonist Causes Weight Loss, Reduces Insulin Resistance, and Improves Cardiovascular Function in Diet-Induced Obese Rhesus Macaques

(2012) P. Kievit et al.   DIABETES

Using ortholog sequence data to predict the functional relevance of mutations in G-protein-coupled receptors

(2012) Maxi Cöster et al.   FASEB JOURNAL

Structure of the human κ-opioid receptor in complex with JDTic

(2012) Huixian Wu et al.   NATURE

Mechanism of N-terminal modulation of activity at the melanocortin-4 receptor GPCR

(2012) Baran A Ersoy et al.   Nature Chemical Biology

Extended and Structurally Supported Insights into Extracellular Hormone Binding, Signal Transduction and Organization of the Thyrotropin Receptor

(2012) Gerd Krause et al.   PLoS One

Single-molecule analysis of fluorescently labeled G-protein-coupled receptors reveals complexes with distinct dynamics and organization

(2012) D. Calebiro et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Crystal Structure of a Lipid G Protein-Coupled Receptor

(2012) M. A. Hanson et al.   SCIENCE

Evidence for activity-regulated hormone-binding cooperativity across glycoprotein hormone receptor homomers

(2012) Maxime Zoenen et al.   Nature Communications

Heteromerization of human cytomegalovirus encoded chemokine receptors

(2011) Pia Tschische et al.   BIOCHEMICAL PHARMACOLOGY

Comparative Fluorescence Resonance Energy Transfer Analysis of Metabotropic Glutamate Receptors

(2011) Masataka Yanagawa et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Full characterization of GPCR monomer–dimer dynamic equilibrium by single molecule imaging

(2011) Rinshi S. Kasai et al.   JOURNAL OF CELL BIOLOGY

Crystal structure of metarhodopsin II

(2011) Hui-Woog Choe et al.   NATURE

G protein-coupled receptors: mutations and endocrine diseases

(2011) Gilbert Vassart et al.   Nature Reviews Endocrinology

History and Biological Significance of GPCR Heteromerization in the Neuroendocrine System

(2011) Kenjiro Tadagaki et al.   NEUROENDOCRINOLOGY

Chemogenomic Analysis of G-Protein Coupled Receptors and Their Ligands Deciphers Locks and Keys Governing Diverse Aspects of Signalling

(2011) Jörg D. Wichard et al.   PLoS One

The Melanocortin-4 Receptor: Physiology, Pharmacology, and Pathophysiology

(2010) Ya-Xiong Tao   ENDOCRINE REVIEWS

Interactions of the Melanocortin-4 Receptor with the Peptide Agonist NDP-MSH

(2010) Kathryn L. Chapman et al.   JOURNAL OF MOLECULAR BIOLOGY

Therapeutic antibodies directed at G protein-coupled receptors

(2010) Catherine J. Hutchings et al.   mAbs

A Structural Insight into the Reorientation of Transmembrane Domains 3 and 5 during Family A G Protein-Coupled Receptor Activation

(2010) K. Sansuk et al.   MOLECULAR PHARMACOLOGY

Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor

(2010) Michael P. Bokoch et al.   NATURE

Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules

(2010) J. A. Hern et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

GPCR Dimers Fall Apart

(2010) N. A. Lambert   Science Signaling

Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation

(2010) M.C. Peeters et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Regulation of Transcription Factors by Heterotrimeric G Proteins

(2010) M. Ho et al.   Current Molecular Pharmacology

Dimerization in GPCR mobility and signaling

(2009) Martin J Lohse   CURRENT OPINION IN PHARMACOLOGY

Pertussis Toxin-sensitive Signaling of Melanocortin-4 Receptors in Hypothalamic GT1-7 Cells Defines Agouti-related Protein as a Biased Agonist

(2009) Thomas R. H. Büch et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation

(2009) Shivani Ahuja et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Heterodimerization of Hypothalamic G-Protein-Coupled Receptors Involved in Weight Regulation

(2009) Anne Rediger et al.   Obesity Facts

Evolution of opsins and phototransduction

(2009) Y. Shichida et al.   PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

A G protein-coupled receptor at work: the rhodopsin model

(2009) Klaus Peter Hofmann et al.   TRENDS IN BIOCHEMICAL SCIENCES

Multiple Switches in G Protein-Coupled Receptor Activation

(2009) Shivani Ahuja et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Ligand binding and micro-switches in 7TM receptor structures

(2009) Rie Nygaard et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Multiple Ca2+-Binding Sites in the Extracellular Domain of the Ca2+-Sensing Receptor Corresponding to Cooperative Ca2+Response†

(2008) Yun Huang et al.   BIOCHEMISTRY

Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors

(2008) M M Rosenkilde et al.   BRITISH JOURNAL OF PHARMACOLOGY

Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor

(2008) Filippo Mancia et al.   EMBO REPORTS

Crystal structure of opsin in its G-protein-interacting conformation

(2008) Patrick Scheerer et al.   NATURE

Crystal structure of the ligand-free G-protein-coupled receptor opsin

(2008) Jung Hee Park et al.   NATURE

Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction

(2008) Jarl E. S. Wikberg et al.   NATURE REVIEWS DRUG DISCOVERY

Constitutive activation of G protein-coupled receptors and diseases: Insights into mechanisms of activation and therapeutics

(2008) Y TAO   PHARMACOLOGY & THERAPEUTICS

Pharmacological analyses of two naturally occurring porcine melanocortin-4 receptor mutations in domestic pigs

(2007) Zhen-Chuan Fan et al.   DOMESTIC ANIMAL ENDOCRINOLOGY