PMID:23202856

Citation	Steiner, S, Lori, C, Boehm, A and Jenal, U (2013) Allosteric activation of exopolysaccharide synthesis through cyclic di-GMP-stimulated protein-protein interaction. EMBO J. 32:354-68
Abstract	In many bacterial pathogens, the second messenger c-di-GMP stimulates the production of an exopolysaccharide (EPS) matrix to shield bacteria from assaults of the immune system. How c-di-GMP induces EPS biogenesis is largely unknown. Here, we show that c-di-GMP allosterically activates the synthesis of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc), a major extracellular matrix component of Escherichia coli biofilms. C-di-GMP binds directly to both PgaC and PgaD, the two inner membrane components of the poly-GlcNAc synthesis machinery to stimulate their glycosyltransferase activity. We demonstrate that the PgaCD machinery is a novel type c-di-GMP receptor, where ligand binding to two proteins stabilizes their interaction and promotes enzyme activity. This is the first example of a c-di-GMP-mediated process that relies on protein-protein interaction. At low c-di-GMP concentrations, PgaD fails to interact with PgaC and is rapidly degraded. Thus, when cells experience a c-di-GMP trough, PgaD turnover facilitates the irreversible inactivation of the Pga machinery, thereby temporarily uncoupling it from c-di-GMP signalling. These data uncover a mechanism of c-di-GMP-mediated EPS control and provide a frame for c-di-GMP signalling specificity in pathogenic bacteria.
Links	PubMed PMC3567491 Online version:10.1038/emboj.2012.315
Keywords	Allosteric Regulation/physiology; Biofilms/growth & development; Cyclic GMP/analogs & derivatives; Cyclic GMP/metabolism; Escherichia coli/growth & development; Escherichia coli/metabolism; Escherichia coli Proteins/metabolism; Extracellular Matrix Proteins/biosynthesis; Glycosyltransferases/metabolism; Immunoblotting; Immunoprecipitation; Models, Molecular; Polysaccharides, Bacterial/biosynthesis; Second Messenger Systems/physiology; beta-Glucans
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ECOLI:PGAD	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P75905	F		Seeded From UniProt	complete
ECOLI:PGAD	located_in	GO:0005887: integral component of plasma membrane	ECO:0000245: automatically integrated combinatorial evidence used in manual assertion		C		Seeded From UniProt	complete
ECOLI:PGAD	involved_in	GO:0043708: cell adhesion involved in biofilm formation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
ECOLI:PGAD	located_in	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
ECOLI:PGAC	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P69432	F		Seeded From UniProt	complete
ECOLI:PGAC	located_in	GO:0005887: integral component of plasma membrane	ECO:0000245: automatically integrated combinatorial evidence used in manual assertion		C		Seeded From UniProt	complete
ECOLI:PGAC	involved_in	GO:0043708: cell adhesion involved in biofilm formation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
ECOLI:PGAC	located_in	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
ECOLI:DGCT	acts_upstream_of_or_within	GO:0090609: single-species submerged biofilm formation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
ECOLI:YCDT	involved_in	GO:0090609: single-species submerged biofilm formation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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