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

Publication ,  Journal Article
Schumacher, MA; Wörmann, ME; Henderson, M; Salinas, R; Latoscha, A; Al-Bassam, MM; Singh, KS; Barclay, E; Gunka, K; Tschowri, N
Published in: Nat Commun
October 3, 2022

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 3, 2022

Volume

13

Issue

1

Start / End Page

5834

Location

England

Related Subject Headings

  • Streptomyces
  • Second Messenger Systems
  • Glycogen
  • Glucose
  • Gene Expression Regulation, Bacterial
  • Cyclic GMP
  • Bacterial Proteins
  • Anti-Bacterial Agents
  • Animals
  • Allosteric Regulation
 

Citation

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Schumacher, M. A., Wörmann, M. E., Henderson, M., Salinas, R., Latoscha, A., Al-Bassam, M. M., … Tschowri, N. (2022). Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP. Nat Commun, 13(1), 5834. https://doi.org/10.1038/s41467-022-33537-w
Schumacher, Maria A., Mirka E. Wörmann, Max Henderson, Raul Salinas, Andreas Latoscha, Mahmoud M. Al-Bassam, Kumar Siddharth Singh, Elaine Barclay, Katrin Gunka, and Natalia Tschowri. “Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP.Nat Commun 13, no. 1 (October 3, 2022): 5834. https://doi.org/10.1038/s41467-022-33537-w.
Schumacher MA, Wörmann ME, Henderson M, Salinas R, Latoscha A, Al-Bassam MM, et al. Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP. Nat Commun. 2022 Oct 3;13(1):5834.
Schumacher, Maria A., et al. “Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP.Nat Commun, vol. 13, no. 1, Oct. 2022, p. 5834. Pubmed, doi:10.1038/s41467-022-33537-w.
Schumacher MA, Wörmann ME, Henderson M, Salinas R, Latoscha A, Al-Bassam MM, Singh KS, Barclay E, Gunka K, Tschowri N. Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP. Nat Commun. 2022 Oct 3;13(1):5834.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 3, 2022

Volume

13

Issue

1

Start / End Page

5834

Location

England

Related Subject Headings

  • Streptomyces
  • Second Messenger Systems
  • Glycogen
  • Glucose
  • Gene Expression Regulation, Bacterial
  • Cyclic GMP
  • Bacterial Proteins
  • Anti-Bacterial Agents
  • Animals
  • Allosteric Regulation