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Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP

Author

Listed:
  • Maria A. Schumacher

    (Duke University School of Medicine)

  • Mirka E. Wörmann

    (Humboldt-Universität zu Berlin
    Bundesinstitut für Risikobewertung)

  • Max Henderson

    (Duke University School of Medicine)

  • Raul Salinas

    (Duke University School of Medicine)

  • Andreas Latoscha

    (Humboldt-Universität zu Berlin)

  • Mahmoud M. Al-Bassam

    (University of California, San Diego)

  • Kumar Siddharth Singh

    (Leibniz Universität Hannover)

  • Elaine Barclay

    (John Innes Centre)

  • Katrin Gunka

    (Leibniz Universität Hannover)

  • Natalia Tschowri

    (Leibniz Universität Hannover)

Abstract

Streptomyces are our principal source of antibiotics, which they generate concomitant with a complex developmental transition from vegetative hyphae to spores. c-di-GMP acts as a linchpin in this transition by binding and regulating the key developmental regulators, BldD and WhiG. Here we show that c-di-GMP also binds the glycogen-debranching-enzyme, GlgX, uncovering a direct link between c-di-GMP and glycogen metabolism in bacteria. Further, we show c-di-GMP binding is required for GlgX activity. We describe structures of apo and c-di-GMP-bound GlgX and, strikingly, their comparison shows c-di-GMP induces long-range conformational changes, reorganizing the catalytic pocket to an active state. Glycogen is an important glucose storage compound that enables animals to cope with starvation and stress. Our in vivo studies reveal the important biological role of GlgX in Streptomyces glucose availability control. Overall, we identify a function of c-di-GMP in controlling energy storage metabolism in bacteria, which is widespread in Actinobacteria.

Suggested Citation

  • Maria A. Schumacher & Mirka E. Wörmann & Max Henderson & Raul Salinas & Andreas Latoscha & Mahmoud M. Al-Bassam & Kumar Siddharth Singh & Elaine Barclay & Katrin Gunka & Natalia Tschowri, 2022. "Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33537-w
    DOI: 10.1038/s41467-022-33537-w
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