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Study · Not a test of the peptide alone · 2021

3 results

Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren.

Liu H, Sun D, Myasnikov A, Damian M, Baneres JL, Sun J, Zhang C

Nature communications4 Nov 2021Cited by 59 (Europe PMC)

PMID34737341 (opens in a new tab)PMCIDPMC8568970 (opens in a new tab)DOI10.1038/s41467-021-26735-5 (opens in a new tab)PepBankPUB-34737341
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Summary

The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its agonistic action on GHSR. Synthetic agonists of GHSR are under clinical evaluation for disorders related to appetite and growth hormone dysregulation. Here, we report high-resolution cryo-EM structures of the GHSR-Gi signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug. Our structures together with mutagenesis data reveal the molecular basis for the binding of ghrelin and ibutamoren. Structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation. Notable structural variations of the Gi and GHSR coupling are observed in our cryo-EM analysis. Our results provide a framework for understanding GHSR signaling and developing new GHSR agonist drugs.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, MK-677 (ibutamoren) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking MK-677 (ibutamoren).

  1. 01LabNot a test of MK-677 (ibutamoren) aloneIn vitro (cell-free)Mechanism

    In structural and mutagenesis analyses, researchers resolved the molecular basis of ibutamoren binding to GHSR.

    In plain wordsIn lab tests, structures and mutation data revealed how ibutamoren binds GHSR.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    Not applicableAgonist binding basis
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Our structures together with mutagenesis data reveal the molecular basis for the binding of ghrelin and ibutamoren.
    1 context sentence
    Summary · context
    Here, we report high-resolution cryo-EM structures of the GHSR-Gi signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug.

    In this study, MK-677 (ibutamoren) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MK-677 (ibutamoren).

  2. 02LabNot a test of MK-677 (ibutamoren) aloneIn vitro (cell-free)Mechanism

    In GHSR structural comparisons, a salt bridge and aromatic cluster near the agonist-binding pocket appeared important for activation.

    In plain wordsIn lab tests, a salt bridge and aromatic cluster near the binding pocket appeared important for receptor activation.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    Not applicableReceptor activation motifs
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation.
    1 context sentence
    Summary · context
    Here, we report high-resolution cryo-EM structures of the GHSR-Gi signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug.

    In this study, MK-677 (ibutamoren) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MK-677 (ibutamoren).

  3. 03LabNot a test of MK-677 (ibutamoren) aloneIn vitro (cell-free)Mechanism

    In cryo-EM analyses of agonist-bound complexes including ibutamoren, researchers observed structural variations in Gi-GHSR coupling.

    In plain wordsIn lab tests, agonist-bound receptor complexes including ibutamoren showed variations in receptor coupling.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    Not applicableGi-GHSR coupling variations
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Notable structural variations of the Gi and GHSR coupling are observed in our cryo-EM analysis.
    1 context sentence
    Summary · context
    Here, we report high-resolution cryo-EM structures of the GHSR-Gi signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug.

    In this study, MK-677 (ibutamoren) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MK-677 (ibutamoren).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

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

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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