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.

c-di-GMP has emerged as the signal controlling development in antibiotic producing Streptomyces. Here the authors describe another developmental role of c-di-GMP, in energy metabolism, by activating the glycogen-debranchingenzyme, GlgX. Structures revealing the activation mechanism are described.

Details

Title
Allosteric regulation of glycogen breakdown by the second messenger cyclic di-GMP
Author
Schumacher, Maria A. 1   VIAFID ORCID Logo  ; Wörmann, Mirka E. 2 ; Henderson, Max 1 ; Salinas, Raul 1 ; Latoscha, Andreas 3   VIAFID ORCID Logo  ; Al-Bassam, Mahmoud M. 4 ; Singh, Kumar Siddharth 5 ; Barclay, Elaine 6 ; Gunka, Katrin 5 ; Tschowri, Natalia 5   VIAFID ORCID Logo 

 Duke University School of Medicine, Department of Biochemistry, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961) 
 Humboldt-Universität zu Berlin, Institute for Biology/Microbiology, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639); Bundesinstitut für Risikobewertung, Berlin, Germany (GRID:grid.417830.9) (ISNI:0000 0000 8852 3623) 
 Humboldt-Universität zu Berlin, Institute for Biology/Microbiology, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639) 
 University of California, San Diego, Department of Pediatrics, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
 Leibniz Universität Hannover, Institute of Microbiology, Hannover, Germany (GRID:grid.9122.8) (ISNI:0000 0001 2163 2777) 
 John Innes Centre, Department of Cell and Developmental Biology, Norwich, UK (GRID:grid.14830.3e) (ISNI:0000 0001 2175 7246) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2720702220
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.