The structure and transcriptional analysis of a global regulator from Neisseria meningitidis

J Biol Chem. 2007 May 11;282(19):14655-64. doi: 10.1074/jbc.M701082200. Epub 2007 Mar 20.

Abstract

Neisseria meningitidis, a causative agent of bacterial meningitis, has a relatively small repertoire of transcription factors, including NMB0573 (annotated AsnC), a member of the Lrp-AsnC family of regulators that are widely expressed in both Bacteria and Archaea. In the present study we show that NMB0573 binds to l-leucine and l-methionine and have solved the structure of the protein with and without bound amino acids. This has shown, for the first time that amino acid binding does not induce significant conformational changes in the structure of an AsnC/Lrp regulator although it does appear to stabilize the octameric assembly of the protein. Transcriptional profiling of wild-type and NMB0573 knock-out strains of N. meningitidis has shown that NMB0573 is associated with an adaptive response to nutrient poor conditions reflected in a reduction in major surface protein expression. On the basis of its structure and the transcriptional response, we propose that NMB0573 is a global regulator in Neisseria controlling responses to nutrient availability through indicators of general amino acid abundance: leucine and methionine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism
  • Crystallization
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Escherichia coli Proteins / chemistry
  • Gene Expression Regulation, Bacterial*
  • Leucine-Responsive Regulatory Protein / chemistry
  • Leucine-Responsive Regulatory Protein / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Neisseria meningitidis / genetics*
  • Neisseria meningitidis / metabolism
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • Archaeal Proteins
  • AsnC protein, E coli
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Lrp protein, E coli
  • Trans-Activators
  • Transcription Factors
  • Leucine-Responsive Regulatory Protein

Associated data

  • PDB/2P5V
  • PDB/2P6S
  • PDB/2P6T