ArticleChemistry & biology2013
Molecular and functional analysis of human β-defensin 3 action at melanocortin receptors.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- Neuro-immuno-endocrinology of the skin: how environment regulates body homeostasis.Nature reviews. Endocrinology · 2025Review
- Review
- Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects.International journal of molecular sciences · 2023Review
- Improving Fmoc Solid Phase Synthesis of Human Beta Defensin 3.International journal of molecular sciences · 2022Article
- Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin.Biomolecules · 2022Review
- Therapies for Membranous Nephropathy: A Tale From the Old and New Millennia.Frontiers in immunology · 2022Review
- Review
- Participation of keratinocyte- and fibroblast-derived factors in melanocyte homeostasis, the response to UV, and pigmentary disorders.Pigment cell & melanoma research · 2021Review
- Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma.International journal of molecular sciences · 2020Review
- cAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.Advances in protein chemistry and structural biology · 2019Review
- Human β-Defensin 1 and β-Defensin 3 (Mouse Ortholog mBD14) Function as Full Endogenous Agonists at Select Melanocortin Receptors.Journal of medicinal chemistry · 2018Article
- The melanocortin signaling cAMP axis accelerates repair and reduces mutagenesis of platinum-induced DNA damage.Scientific reports · 2017Article
- Article
- A Life without Hunger: The Ups (and Downs) to Modulating Melanocortin-3 Receptor Signaling.Frontiers in neuroscience · 2017Review
- Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor heterogeneity and increases survival.Oncotarget · 2016Article
- 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH.Journal of molecular endocrinology · 2016Review
- Melanocortin 1 Receptor: Structure, Function, and Regulation.Frontiers in genetics · 2016Review
- An ancestral host defence peptide within human β-defensin 3 recapitulates the antibacterial and antiviral activity of the full-length molecule.Scientific reports · 2015Article
- Defining the Contribution of MC1R Physiological Ligands to ATR Phosphorylation at Ser435, a Predictor of DNA Repair in Melanocytes.The Journal of investigative dermatology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The β-defensins are a class of small, cationic proteins first recognized as antimicrobial components of the innate and adaptive immune system. More recently, one of the major β-defensins produced in skin, β-defensin 3, has been discovered to function as a melanocortin receptor ligand in vivo and in vitro, but its biophysical and pharmacological basis of action has been enigmatic. Here, we report functional and biochemical studies focused on human β-defensin 3 (HBD3) and melanocortin receptors 1 and 4. Genetic and pharmacologic studies indicate that HBD3 acts as a neutral melanocortin receptor antagonist capable of blocking the action of either stimulatory agonists such as α-melanocyte stimulating hormone or inhibitory inverse agonists such as Agouti signaling protein (ASIP) and Agouti-related protein (AGRP). A comprehensive structure-function analysis demonstrates that two patches of positively charged residues, located on opposite poles of HBD3 and spatially organized by the compact β-defensin fold, are primarily responsible for high-affinity binding to melanocortin receptors. These findings identify a distinct mode of melanocortin receptor-ligand interactions based primarily on electrostatic complementarity, with implications for designing ligands that target melanocortin and potentially other seven transmembrane receptors.
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Registered trials
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 OpenQuestion graph.