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Molecular Pharmacology

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Research ArticleArticle

Chimeric Melanocortin MC1 and MC3 Receptors: Identification of Domains Participating in Binding of Melanocyte-Stimulating Hormone Peptides

Helgi B. Schiöth, Philip Yook, Ruta Muceniece, Jarl E. S. Wikberg and Michael Szardenings
Molecular Pharmacology July 1998, 54 (1) 154-161; DOI: https://doi.org/10.1124/mol.54.1.154
Helgi B. Schiöth
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Philip Yook
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Ruta Muceniece
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Jarl E. S. Wikberg
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Michael Szardenings
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Abstract

The melanocortin receptors MC1 and MC3 are G protein-coupled receptors that have substantial structural similarities and bind melanocyte peptides but with different affinity profiles. We constructed a series of chimeric MC1/MC3 receptors to identify the epitopes that determine their selectivities for natural melanocyte peptides and synthetic analogues. The chimeric constructs were made by a polymerase chain reaction that used identical regions in or just outside transmembranes (TM) 1, 4, and 6 and divided the receptors into four segments. Saturation and competition studies on the expressed chimeric proteins indicate that TM1, TM2, TM3, and TM7 are involved in the subtype-specific binding of melanocyte peptides to these receptors. The results support the hypothesis that TM4 and TM5 may not contribute to the ligand-binding specificity of the MC receptors. This is the first report to describe the subtype-specific hormone-binding domains of the melanocortin receptor family.

Footnotes

    • Received August 22, 1997.
    • Accepted March 9, 1998.
  • Send reprint requests to: Dr. Michael Szardenings or Dr. Jarl E. S. Wikberg, Department of Pharmaceutical Pharmacology, Biomedical Center, Box 591, 751 24 Uppsala, Sweden. E-mail:msz{at}bmc.uu.se orjarl.wikberg{at}farmbio.uu.se

  • This work was supported by grants from the Swedish Medical Research Council (04X-05957), the Swedish Centrala Forsoksdjurs Namnden, the Groschinsky, Bergwall, and Wiberg foundations, the Royal Swedish Academy of Science, the Howard Hughes Medical Institute (HHMI 75195–548501), and the Swedish Society for Medical Research.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 54 (1)
Molecular Pharmacology
Vol. 54, Issue 1
1 Jul 1998
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Research ArticleArticle

Chimeric Melanocortin MC1 and MC3 Receptors: Identification of Domains Participating in Binding of Melanocyte-Stimulating Hormone Peptides

Helgi B. Schiöth, Philip Yook, Ruta Muceniece, Jarl E. S. Wikberg and Michael Szardenings
Molecular Pharmacology July 1, 1998, 54 (1) 154-161; DOI: https://doi.org/10.1124/mol.54.1.154

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Research ArticleArticle

Chimeric Melanocortin MC1 and MC3 Receptors: Identification of Domains Participating in Binding of Melanocyte-Stimulating Hormone Peptides

Helgi B. Schiöth, Philip Yook, Ruta Muceniece, Jarl E. S. Wikberg and Michael Szardenings
Molecular Pharmacology July 1, 1998, 54 (1) 154-161; DOI: https://doi.org/10.1124/mol.54.1.154
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