Structure of a transiently phosphorylated switch in bacterial signal transduction.
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.
Kern
D
D
Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA. dkern@brandeis.edu
Volkman
B F
BF
Luginbühl
P
P
Nohaile
M J
MJ
Kustu
S
S
Wemmer
D E
DE
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
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D051922:PII Nitrogen Regulatory Proteins; D015534:Trans-Activators; D014157:Transcription Factors