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Biological effects of the loss of homochirality in a multicellular organism

Author

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  • Agnes Banreti

    (Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose)

  • Shayon Bhattacharya

    (University of Limerick)

  • Frank Wien

    (DISCO Beamline, Synchrotron SOLEIL)

  • Koichi Matsuo

    (Hiroshima University)

  • Matthieu Réfrégiers

    (Centre de Biophysique Moléculaire)

  • Cornelia Meinert

    (Université Côte d’Azur, Institut de Chimie de Nice)

  • Uwe Meierhenrich

    (Université Côte d’Azur, Institut de Chimie de Nice)

  • Bruno Hudry

    (Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose)

  • Damien Thompson

    (University of Limerick)

  • Stéphane Noselli

    (Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose)

Abstract

Homochirality is a fundamental feature of all known forms of life, maintaining biomolecules (amino-acids, proteins, sugars, nucleic acids) in one specific chiral form. While this condition is central to biology, the mechanisms by which the adverse accumulation of non-l-α-amino-acids in proteins lead to pathophysiological consequences remain poorly understood. To address how heterochirality build-up impacts organism’s health, we use chiral-selective in vivo assays to detect protein-bound non-l-α-amino acids (focusing on aspartate) and assess their functional significance in Drosophila. We find that altering the in vivo chiral balance creates a ‘heterochirality syndrome’ with impaired caspase activity, increased tumour formation, and premature death. Our work shows that preservation of homochirality is a key component of protein function that is essential to maintain homeostasis across the cell, tissue and organ level.

Suggested Citation

  • Agnes Banreti & Shayon Bhattacharya & Frank Wien & Koichi Matsuo & Matthieu Réfrégiers & Cornelia Meinert & Uwe Meierhenrich & Bruno Hudry & Damien Thompson & Stéphane Noselli, 2022. "Biological effects of the loss of homochirality in a multicellular organism," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34516-x
    DOI: 10.1038/s41467-022-34516-x
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    References listed on IDEAS

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    1. Craig A. Micchelli & Norbert Perrimon, 2006. "Evidence that stem cells reside in the adult Drosophila midgut epithelium," Nature, Nature, vol. 439(7075), pages 475-479, January.
    2. Gongyu Li & Kellen DeLaney & Lingjun Li, 2019. "Molecular basis for chirality-regulated Aβ self-assembly and receptor recognition revealed by ion mobility-mass spectrometry," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    3. Rebeccah A. Warmack & David R. Boyer & Chih-Te Zee & Logan S. Richards & Michael R. Sawaya & Duilio Cascio & Tamir Gonen & David S. Eisenberg & Steven G. Clarke, 2019. "Structure of amyloid-β (20-34) with Alzheimer’s-associated isomerization at Asp23 reveals a distinct protofilament interface," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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