Structure of a transiently phosphorylated switch in bacterial signal transduction. Nature 1999 Dec 23-30;402(6764):894-8
Date
01/06/2000Pubmed ID
10622255DOI
10.1038/47273Scopus ID
2-s2.0-0033599026 (requires institutional sign-in at Scopus site) 180 CitationsAbstract
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.
Author List
Kern D, Volkman BF, Luginbühl P, Nohaile MJ, Kustu S, Wemmer DEAuthor
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Bacterial ProteinsBinding Sites
DNA-Binding Proteins
Magnetic Resonance Spectroscopy
Models, Molecular
PII Nitrogen Regulatory Proteins
Phosphorylation
Protein Conformation
Signal Transduction
Trans-Activators
Transcription Factors
