The orphan histidine protein kinase SgmT is a c‐di‐GMP receptor and regulates composition of the extracellular matrix together with the orphan DNA binding response regulator DigR in Myxococcus xanthus

Abstract

In Myxococcus xanthus the extracellular matrix is essential for type IV pili-dependent motility and starvation-induced fruiting body formation. Proteins of two-component systems including the orphan DNA binding response regulator DigR are essential in regulating the composition of the extracellular matrix. We identify the orphan hybrid histidine kinase SgmT as the partner kinase of DigR. In addition to kinase and receiver domains, SgmT consists of an N-terminal GAF domain and a C-terminal GGDEF domain. The GAF domain is the primary sensor domain. The GGDEF domain binds the second messenger bis-(3′-5′)-cyclic-dimeric-GMP (c-di-GMP) and functions as a c-di-GMP receptor to spatially sequester SgmT. We identify the DigR binding site in the promoter of the fibA gene, which encodes an abundant extracellular matrix metalloprotease. Whole-genome expression profiling experiments in combination with the identified DigR binding site allowed the identification of the DigR regulon and suggests that SgmT/DigR regulates the expression of genes for secreted proteins and enzymes involved in secondary metabolite synthesis. We suggest that SgmT/DigR regulates extracellular matrix composition and that SgmT activity is regulated by two sensor domains with ligand binding to the GAF domain resulting in SgmT activation and c-di-GMP binding to the GGDEF domain resulting in spatial sequestration of SgmT.

A Cyclic di-GMP-binding Adaptor Protein Interacts with Histidine Kinase to Regulate Two-component Signaling

“…SgmT has a C-terminal non-enzymatic GGDEF domain that functions as a c-di-GMP-binding effector. The binding of c-di-GMP to the GGDEF domain is crucial for the spatial sequestration, and likely cellular function of SgmT (64). The current study suggests that another way for c-di-GMP to control histidine kinase is by using a discrete PilZ adaptor.…”

Coordinated Cyclic-Di-GMP Repression of Salmonella Motility through YcgR and Cellulose

“…Many GGDEF domain proteins harbor a c-di-GMP binding I site that serves as a control point of their own activity through a product inhibition mechanism. Also, enzymatically inactive GGDEF domain proteins may function as c-di-GMP receptors through their I sites, leading to a spatial sequestration of the protein (23,24). Thus, we hypothesized that one or more GGDEF domain proteins of Salmonella might bind c-di-GMP under excess conditions of this nucleotide and then act as direct negative effectors, leading to a blockage of cell motility in the absence of YcgR.…”

“…In agreement with the variety of c-di-GMP-related outputs, the nature of the c-di-GMP binding molecules is diverse. These include the PilZ domain-containing proteins (22), enzymatically inactive GGDEF proteins that contain a degenerate GGDEF domain but a conserved intact I site (23,24), enzymatically inactive EAL proteins which retain the ability to bind c-di-GMP but no longer hydrolyze it (25)(26)(27), PelD from P. aeruginosa, which binds c-di-GMP through an RxxD motif resembling an I site found in active DGCs (28), transcription factors that do not share a predictable c-di-GMP binding site (29)(30)(31)(32)(33)(34)(35)(36), the Escherichia coli polynucleotide phosphorylase (37), and riboswitches (38)(39)(40)(41).…”

PhpA, a tyrosine phosphatase of Myxococcus xanthus, is involved in the production of exopolysaccharide

“…Also, many other proteins are likely to play minor regulatory roles in M. xanthus EPS production (Berleman et al, 2011;Black et al, 2006;Dana & Shimkets, 1993;Kimura et al, 2004;Petters et al, 2012;Weimer et al, 1998). BY kinases have been found to phosphorylate heat shock sigma factors and single-stranded DNA-binding proteins other than enzymes involved in the synthesis of EPS.…”