Cell-free protein production and labeling protocol for NMR-based structural proteomics

Nat Methods. 2004 Nov;1(2):149-53. doi: 10.1038/nmeth716. Epub 2004 Oct 21.

Abstract

Structural proteomics requires robust, scalable methods. Here we describe a wheat germ cell-free platform for protein production that supports efficient NMR structural studies of eukaryotic proteins and offers advantages over cell-based methods. To illustrate this platform, we describe its application to a specific target (At3g01050.1) from Arabidopsis thaliana. After cloning the target gene into a specialized plasmid, we carry out a small-scale (50 mul) in vitro sequential transcription and translation trial to ascertain the level of protein production and solubility. Next, we prepare mRNA for use in a 4-ml semicontinuous cell-free translation reaction to incorporate (15)N-labeled amino acids into a protein sample that we purify and test for suitability for NMR structural analysis. We then repeat the cell-free approach with (13)C,(15)N-labeled amino acids to prepare a doubly labeled sample. The three-dimensional (3D) structure of At3g01050.1 shows that this protein is an unusual member of the beta-grasp protein family.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Arabidopsis Proteins / analysis
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Carbon Isotopes
  • Cell-Free System / metabolism*
  • Computer Simulation
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Plant / physiology
  • Isotope Labeling / methods*
  • Magnetic Resonance Spectroscopy / methods*
  • Models, Chemical
  • Nitrogen Isotopes
  • Protein Conformation
  • Proteome / analysis
  • Proteome / chemistry
  • Proteome / metabolism
  • Proteomics / methods*
  • Sequence Analysis, Protein / methods*
  • Structure-Activity Relationship

Substances

  • Arabidopsis Proteins
  • Carbon Isotopes
  • Nitrogen Isotopes
  • Proteome