title: 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.
authors.affiliation: Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch Str. 10, 35043 Marburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Petters
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Jutta
authors.initials: J
authors.lastname: Nesper
authors.forename: Anke
authors.initials: A
authors.lastname: Treuner-Lange
authors.forename: Nuria
authors.initials: N
authors.lastname: Gomez-Santos
authors.forename: Michael
authors.initials: M
authors.lastname: Hoppert
authors.forename: Urs
authors.initials: U
authors.lastname: Jenal
authors.forename: Lotte
authors.initials: L
authors.lastname: Søgaard-Andersen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D016941:Myxococcus xanthus / Q000201:enzymology* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018085:Regulon
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C022994:cyclic GMP-binding protein; C062025:bis(3',5')-cyclic diguanylic acid; D011494:Protein Kinases; D000071677:Histidine Kinase; D006152:Cyclic GMP