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

authored by
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
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.

Organisation(s)
Institute of Microbiology
External Organisation(s)
Duke University
Humboldt-Universität zu Berlin (HU Berlin)
Federal Institute for Risk Assessment (BfR)
University of California at San Diego
John Innes Centre
Type
Article
Journal
Nature Communications
Volume
13
ISSN
2041-1723
Publication date
12.2022
Publication status
Published
Peer reviewed
Yes
ASJC Scopus subject areas
General Chemistry, General Biochemistry,Genetics and Molecular Biology, General, General Physics and Astronomy
Electronic version(s)
https://doi.org/10.1038/s41467-022-33537-w (Access: Open)