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Study · Not a test of the peptide alone · 2022

3 results

Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation.

Zhai X, Mao C, Shen Q, Zang S, Shen DD, Zhang H, Chen Z, Wang G, Zhang C, Zhang Y, Liu Z

Nature communications21 Oct 2022Cited by 26 (Europe PMC)

PMID36271004 (opens in a new tab)PMCIDPMC9586930 (opens in a new tab)DOI10.1038/s41467-022-34009-x (opens in a new tab)PepBankPUB-36271004
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Summary

The parathyroid hormone type 1 receptor (PTH1R), a class B1 G protein-coupled receptor, plays critical roles in bone turnover and Ca2+ homeostasis. Teriparatide (PTH) and Abaloparatide (ABL) are terms as long-acting and short-acting peptide, respectively, regarding their marked duration distinctions of the downstream signaling. However, the mechanistic details remain obscure. Here, we report the cryo-electron microscopy structures of PTH- and ABL-bound PTH1R-Gs complexes, adapting similar overall conformations yet with notable differences in the receptor ECD regions and the peptide C-terminal portions. 3D variability analysis and site-directed mutagenesis studies uncovered that PTH-bound PTH1R-Gs complexes display less motions and are more tolerant of mutations in affecting the receptor signaling than ABL-bound complexes. Furthermore, we combined the structural analysis and signaling assays to delineate the molecular basis of the differential signaling durations induced by these peptides. Our study deepens the mechanistic understanding of ligand-mediated prolonged or transient signaling.
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, Abaloparatide (Tymlos) 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 Abaloparatide (Tymlos).

  1. 01LabNot a test of Abaloparatide (Tymlos) aloneIn vitro (cells)Mechanism

    Mutagenesis studies showed less tolerance of signaling-altering mutations in abaloparatide-bound complexes than in PTH-bound complexes.

    In plain wordsIn cells, abaloparatide receptor signaling tolerated mutations less than PTH receptor signaling.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    DecreaseTolerance of receptor mutations
    Study

    n: not reported in source

    PTH1R-Gs complexes
    Comparator
    PTH-bound complexes
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    3D variability analysis and site-directed mutagenesis studies uncovered that PTH-bound PTH1R-Gs complexes display less motions and are more tolerant of mutations in affecting the receptor signaling than ABL-bound complexes.

    In this study, Abaloparatide (Tymlos) 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 Abaloparatide (Tymlos).

  2. 02LabNot a test of Abaloparatide (Tymlos) aloneIn vitro (cell-free)Mechanism

    Abaloparatide-bound and PTH-bound receptor complexes had similar overall conformations but differed in receptor extracellular domains and peptide C-terminal portions.

    In plain wordsIn lab tests, abaloparatide and PTH receptor complexes had similar overall shapes but differed in specific regions.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    MixedReceptor complex conformation
    Study

    n: not reported in source

    PTH1R-Gs complexes
    Comparator
    PTH-bound complexes
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Here, we report the cryo-electron microscopy structures of PTH- and ABL-bound PTH1R-Gs complexes, adapting similar overall conformations yet with notable differences in the receptor ECD regions and the peptide C-terminal portions.

    In this study, Abaloparatide (Tymlos) 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 Abaloparatide (Tymlos).

  3. 03Computer modelNot a test of Abaloparatide (Tymlos) aloneIn silicoMechanism

    Structural variability analysis showed greater motion in abaloparatide-bound receptor complexes than in PTH-bound complexes.

    In plain wordsIn computer analyses, abaloparatide receptor complexes moved more than PTH receptor complexes.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    IncreaseReceptor complex motion
    Study

    n: not reported in source

    PTH1R-Gs complexes
    Comparator
    PTH-bound complexes
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    3D variability analysis and site-directed mutagenesis studies uncovered that PTH-bound PTH1R-Gs complexes display less motions and are more tolerant of mutations in affecting the receptor signaling than ABL-bound complexes.

    In this study, Abaloparatide (Tymlos) 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 Abaloparatide (Tymlos).

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

    22 Oct 2026, 02:25 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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