title: Structure of a transiently phosphorylated switch in bacterial signal transduction.
abstract: Receiver domains are the dominant molecular switches in bacterial signalling. Although several structures of non-phosphorylated receiver domains have been reported, a detailed structural understanding of the activation arising from phosphorylation has been impeded by the very short half-lives of the aspartylphosphate linkages. Here we present the first structure of a receiver domain in its active state, the phosphorylated receiver domain of the bacterial enhancer-binding protein NtrC (nitrogen regulatory protein C). Nuclear magnetic resonance spectra were taken during steady-state autophosphorylation/dephosphorylation, and three-dimensional spectra from multiple samples were combined. Phosphorylation induces a large conformational change involving a displacement of beta-strands 4 and 5 and alpha-helices 3 and 4 away from the active site, a register shift and an axial rotation in helix 4. This creates an exposed hydrophobic surface that is likely to transmit the signal to the transcriptional activation domain.
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA. dkern@brandeis.edu
authors.forename: D
authors.initials: D
authors.lastname: Kern
authors.forename: B F
authors.initials: BF
authors.lastname: Volkman
authors.forename: P
authors.initials: P
authors.lastname: Luginbühl
authors.forename: M J
authors.initials: MJ
authors.lastname: Nohaile
authors.forename: S
authors.initials: S
authors.lastname: Kustu
authors.forename: D E
authors.initials: DE
authors.lastname: Wemmer
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D051922:PII Nitrogen Regulatory Proteins; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D051922:PII Nitrogen Regulatory Proteins; D015534:Trans-Activators; D014157:Transcription Factors