ArticleCell research2021
Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor.
Article in Cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- Ultrarapid MC1R protein and associated plumage color evolution in the domestic chicken.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The anti-inflammatory efficacy of melanocortin drugs is influenced by genetic variation at MC1R.Scientific reports · 2026Article
- Tilapia Skin-Derived Peptide PFRMY Attenuates Melanogenesis and Tyrosinase Activity via α-MSH/PKA/CREB Signaling Pathways in B16F10 Murine Melanoma Cells.Foods (Basel, Switzerland) · 2026Article
- Associations of MC1R Substitutions With Body Color Variation in a Desert Lizard.Ecology and evolution · 2026Article
- Metalloprotein-Based Nanomedicines: Design Strategies, Functional Mechanisms, and Biomedical Applications.International journal of molecular sciences · 2026Review
- Physical exercise increases binding of POMC to blood extracellular vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Recommended Tool Compounds for the Melanocortin Receptor (MCR) G Protein-Coupled Receptors (GPCRs).ACS pharmacology & translational science · 2024Article
- Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Identification of oleic acid as an endogenous ligand of GPR3.Cell research · 2024Article
- Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors.Cell discovery · 2023Article
- Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects.International journal of molecular sciences · 2023Review
- Cryo-EM structure of the human chemerin receptor 1-Gi protein complex bound to the C-terminal nonapeptide of chemerin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Buckle up! How the nano-seatbelt MRAP1 fastens ACTH in its orthosteric seat.Cell research · 2023Article
- Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation.Nature communications · 2023Article
- A novel heterozygote allele in caprine melanocortin 1 receptor (MC1R) gene: an association with heat stress traits.Tropical animal health and production · 2023Article
- Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4).Nature communications · 2023Article
- In Vitro, In Vivo, and In Silico Analyses of Molecular Anti-Pigmentation Mechanisms of Selected Thai Rejuvenating Remedy and Bioactive Metabolites.Molecules (Basel, Switzerland) · 2023Article
- Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1.Cell research · 2023Article
- Insights into divalent cation regulation and GCell discovery · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanocortins are peptide hormones critical for the regulation of stress response, energy homeostasis, inflammation, and skin pigmentation. Their functions are mediated by five G protein-coupled receptors (MC1R-MC5R), predominately through the stimulatory G protein (Gs). MC1R, the founding member of melanocortin receptors, is mainly expressed in melanocytes and is involved in melanogenesis. Dysfunction of MC1R is associated with the development of melanoma and skin cancer. Here we present three cryo-electron microscopy structures of the MC1R-Gs complexes bound to endogenous hormone α-MSH, a marketed drug afamelanotide, and a synthetic agonist SHU9119. These structures reveal the orthosteric binding pocket for the conserved HFRW motif among melanocortins and the crucial role of calcium ion in ligand binding. They also demonstrate the basis of differential activities among different ligands. In addition, unexpected interactions between MC1R and the Gβ subunit were discovered from these structures. Together, our results elucidate a conserved mechanism of calcium-mediated ligand recognition, a specific mode of G protein coupling, and a universal activation pathway of melanocortin receptors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.