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Study · In vitro (cells) · 1999

2 results

Conformation of the core sequence in melanocortin peptides directs selectivity for the melanocortin MC3 and MC4 receptors.

Oosterom J, Nijenhuis WA, Schaaper WM, Slootstra J, Meloen RH, Gispen WH, Burbach JP, Adan RA

The Journal of biological chemistry1 Jun 1999Cited by 46 (Europe PMC)

PMID10358030 (opens in a new tab)DOI10.1074/jbc.274.24.16853 (opens in a new tab)PepBankPUB-10358030
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Summary

Melanocortin peptides regulate a variety of physiological processes. Five melanocortin receptors (MC-R) have been cloned and the MC3R and MC4R are the main brain MC receptors. The aim of this study was to identify structural requirements in both ligand and receptor that determine gamma-melanocyte-stimulating hormone (MSH) selectivity for the MC3R versus the MC4R. Substitution of Asp10 in [Nle4]Lys-gamma2-MSH for Gly10 from [Nle4]alpha-MSH, increased both activity and affinity for the MC4R while the MC3R remained unaffected. Analysis of chimeric MC3R/MC4Rs and mutant MC4Rs showed that Tyr268 of the MC4R mainly determined the low affinity for [Nle4]Lys-gamma2-MSH. The data demonstrate that Asp10 determines selectivity for the MC3R, however, not through direct side chain interactions, but probably by influencing how the melanocortin core sequence is presented to the receptor-binding pocket. This is supported by mutagenesis of Tyr268 to Ile in the MC4R which increased affinity and activity for [Nle4]Lys-gamma2-MSH, but decreased affinity for two peptides with constrained cyclic structure of the melanocortin core sequence, MT-II and [D-Tyr4]MT-II, that also displayed lower affinity for the MC3R. This study provides a general concept for peptide receptor selectivity, in which the major determinant for a selective receptor interaction is the conformational presentation of the core sequence in related peptides to the receptor-binding pocket.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Activity measurement

    In cells with the Tyr268-to-Ile mutant MC4R, affinity for MT-II decreased.

    In plain wordsIn cells, changing one amino acid of the MC4R receptor lowered its binding to MT-II.

    Peptide
    Melanotan II
    Outcome
    DecreaseMT-II affinity at the Tyr268Ile mutant MC4R
    Study

    n: not reported in source

    Mutant MC4R (Tyr268 to Ile)
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    mutagenesis of Tyr268 to Ile in the MC4R which increased affinity and activity for [Nle4]Lys-gamma2-MSH, but decreased affinity for two peptides with constrained cyclic structure of the melanocortin core sequence, MT-II and [D-Tyr4]MT-II
  2. 02LabIn vitro (cells)Activity measurement

    In receptor-binding tests, MT-II displayed lower affinity for the MC3R.

    In plain wordsIn lab tests, MT-II bound the MC3R receptor less strongly.

    Peptide
    Melanotan II
    Outcome
    Not applicableMT-II affinity at the MC3R
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MT-II and [D-Tyr4]MT-II, that also displayed lower affinity for the MC3R.

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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