Cell-free protein synthesis in an autoinduction system for NMR studies of protein-protein interactions

J Biomol NMR. 2005 Jul;32(3):235-41. doi: 10.1007/s10858-005-7946-4.

Abstract

Cell-free protein synthesis systems provide facile access to proteins in a nascent state that enables formation of soluble, native protein-protein complexes even if one of the protein components is prone to self-aggregation and precipitation. Combined with selective isotope-labeling, this allows the rapid analysis of protein-protein interactions with few 15N-HSQC spectra. The concept is demonstrated with binary and ternary complexes between the chi, psi and gamma subunits of Escherichia coli DNA polymerase III: nascent, selectively 15N-labeled psi produced in the presence of chi resulted in a soluble, correctly folded chi-psi complex, whereas psi alone precipitated irrespective of whether gamma was present or not. The 15N-HSQC spectra showed that the N-terminal segment of psi is mobile in the chi-psi complex, yet important for its binding to gamma. The sample preparation was greatly enhanced by an autoinduction strategy, where the T7 RNA polymerase needed for transcription of a gene in a T7-promoter vector was produced in situ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell-Free System
  • DNA Polymerase III / chemistry
  • DNA Polymerase III / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Magnetic Resonance Spectroscopy / methods
  • Protein Binding
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Proteins / chemistry
  • Proteins / metabolism*
  • Sensitivity and Specificity

Substances

  • Escherichia coli Proteins
  • Protein Subunits
  • Proteins
  • DNA Polymerase III