GGDEF

GGDEF is a conserved protein domain found in bacteria, named for the characteristic GGDEF amino acid motif within the domain. It functions as the catalytic module of many diguanylate cyclases (DGCs), enzymes that synthesize the bacterial second messenger cyclic di-GMP (c-di-GMP) from two GTP molecules.

Biochemical role and outputs: The product, c-di-GMP, regulates transitions between motile and sessile lifestyles. High c-di-GMP levels generally promote biofilm formation and exopolysaccharide production, while low levels favor motility and dispersal. The exact effects are context-dependent and vary across species.

Structure and regulation: GGDEF domains are often part of multidomain proteins, frequently fused to sensory input modules (such as PAS, GAF) or paired with an EAL or HD-GYP domain that degrades c-di-GMP. The activity of the GGDEF domain is controlled by regulatory cues transmitted through these associated domains. The active site includes the conserved GGDEF motif; product inhibition is commonly achieved via an I-site with the RxxD motif that binds c-di-GMP, providing feedback regulation.

Diversity and activity: Not all GGDEF domains are catalytically active; some are degenerate and function as regulators or scaffolds. In many bacteria, multiple DGC and phosphodiesterase enzymes together shape intracellular c-di-GMP levels, coordinating surface attachment, motility, and virulence traits.