title: The cytoplasmic PASC domain of the sensor kinase DcuS of Escherichia coli: role in signal transduction, dimer formation, and DctA interaction.
abstract: The cytoplasmic PASC domain of the fumarate responsive sensor kinase DcuS of Escherichia coli links the transmembrane to the kinase domain. PASC is also required for interaction with the transporter DctA serving as a cosensor of DcuS. Earlier studies suggested that PASC functions as a hinge and transmits the signal to the kinase. Reorganizing the PASC dimer interaction and, independently, removal of DctA, converts DcuS to the constitutive ON state (active without fumarate stimulation). ON mutants were categorized with respect to these two biophysical interactions and the functional state of DcuS: type I-ON mutations grossly reorganize the homodimer, and decrease interaction with DctA. Type IIA-ON mutations create the ON state without grossly reorganizing the homodimer, whereas interaction with DctA is decreased. The type IIB-ON mutations were neither in PASC /PASC , nor in DctA/DcuS interaction affected, similar to fumarate activated wild-typic DcuS. OFF mutations never affected dimer stability. The ON mutations provide novel mechanistic insight: PASC dimerization is essential to silence the kinase. Reorganizing the homodimer and its interaction with DctA activate the kinase. The study suggests a novel ON homo-dimer conformation (type IIB) and an OFF conformation for PASC . Type IIB-ON corresponds to the fumarate induced wild-type conformation, representing an interesting target for structural biology.
authors.affiliation: Institute for Microbiology and Wine Research, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Monzel
authors.forename: Pia
authors.initials: P
authors.lastname: Degreif-Dünnwald
authors.forename: Christina
authors.initials: C
authors.lastname: Gröpper
authors.forename: Christian
authors.initials: C
authors.lastname: Griesinger
authors.forename: Gottfried
authors.initials: G
authors.lastname: Unden
mesh_terms: D004252:DNA Mutational Analysis; D029382:Dicarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D015398:Signal Transduction
chemical_list: C000589721:DctA protein, E coli; D029382:Dicarboxylic Acid Transporters; D029968:Escherichia coli Proteins; D011494:Protein Kinases; C469359:DcuS protein, E coli
keywords: DctA; DcuS sensor kinase; PAS domain; fumarate; signal transduction.
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