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PMID:23202856

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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

Significance

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

Notes

See also

References

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