title: Modulation of the Rcs-mediated signal transfer by conformational flexibility.
abstract: The Rcs (regulator of capsule synthesis) signalling complex comprises the membrane-associated hybrid sensor kinases RcsC and RcsD, the transcriptional regulator RcsB and the two co-inducers RcsA and RcsF. Acting as a global regulatory network, the Rcs phosphorelay controls multiple cellular pathways including capsule synthesis, cell division, motility, biofilm formation and virulence mechanisms. Signal-dependent communication of the individual Rcs domains showing histidine kinase, phosphoreceiver, phosphoryl transfer and DNA-binding activities is characteristic and essential for the modulation of signal transfer. We have analysed the structures of core elements of the Rcs network including the RcsC-PR (phosphoreceiver domain of RcsC) and the RcsD-HPt (histidine phosphotransfer domain of RcsD), and we have started to characterize the dynamics and recognition mechanisms of the proteins. RcsC-PR represents a typical CheY-like alpha/beta/alpha sandwich fold and it shows a large conformational flexibility near the active-site residue Asp(875). NMR analysis revealed that RcsC-PR is able to adopt preferred conformations upon Mg(2+) co-ordination, BeF(3)(-) activation, phosphate binding and RcsD-HPt recognition. In contrast, the alpha-helical structure of RcsD-HPt is conformationally stable and contains a recognition area in close vicinity to the active-site His(842) residue. Our studies indicate the importance of protein dynamics and conformational exchange for the differential response to the variety of signals perceived by complex regulatory networks.
authors.affiliation: Institute of Biophysical Chemistry and Centre for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany. rogov@bpc.uni-frankfurt.de
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Rogov
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schmöe
authors.forename: Fank
authors.initials: F
authors.lastname: Löhr
authors.forename: Natalia Yu
authors.initials: NY
authors.lastname: Rogova
authors.forename: Frank
authors.initials: F
authors.lastname: Bernhard
authors.forename: Volker
authors.initials: V
authors.lastname: Dötsch
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D018583:Pliability / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D008274:Magnesium