Structure of a transiently phosphorylated switch in bacterial signal transduction

Nature. 1999 Dec 23-30;402(6764):894-8. doi: 10.1038/47273.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • PII Nitrogen Regulatory Proteins
  • Phosphorylation
  • Protein Conformation
  • Signal Transduction*
  • Trans-Activators*
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • PII Nitrogen Regulatory Proteins
  • Trans-Activators
  • Transcription Factors

Associated data

  • PDB/1DC7
  • PDB/1DC8