Integration of electrokinetic-based multidimensional separation/concentration platform with electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry for proteome analysis of Shewanella oneidensis

Anal Chem. 2003 Sep 1;75(17):4432-40. doi: 10.1021/ac0342572.

Abstract

This work focuses on the development of a multidimensional electrokinetic-based separation/concentration platform coupled with electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) for achieving the high resolution and ultrasensitive analysis of complex protein/peptide mixtures. A microdialysis junction is employed as the interface for on-line combination of capillary isoelectric focusing (CIEF) with transient capillary isotachophoresis/zone electrophoresis (CITP/CZE) in an integrated platform. Besides the excellent resolving power afforded by both CIEF and CZE separations, the electrokinetic focusing/stacking effects of CIEF and CITP greatly enhance the dynamic range and detection sensitivity of MS for protein identification. The constructed multidimensional separation/concentration platform is demonstrated for the analysis of Shewanella oneidensis proteome, which has considerable implications toward the bioremediation of environmental pollutants. The electrokinetic-based platform offers the overall peak capacity comparable to those obtained using multidimensional chromatography systems, but with a much shorter run time and no need for column regeneration. Most importantly, a total of 1174 unique proteins, corresponding to 26.5% proteome coverage, are identified from the cytosolic fraction of S. oneidensis, while requiring <500 ng of proteolytic digest loaded in the CIEF capillary. The ultrasensitive capabilities of electrokinetic-based proteome approach are attributed to the concentration effect in CIEF, the electrokinetic stacking of CITP, the nanoscale peak volume in CZE, the "accurate mass tag" strategy for protein/peptide identification, and the high-sensitivity, high-resolution, and high-mass measurement accuracy of FTICR-MS.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / analysis*
  • Cattle
  • Cyclotrons
  • Electrochemistry
  • Electrophoresis, Capillary
  • Electrophoresis, Gel, Two-Dimensional
  • Fourier Analysis
  • Isoelectric Focusing
  • Kinetics
  • Molecular Sequence Data
  • Proteome / analysis*
  • Serum Albumin, Bovine / analysis
  • Serum Albumin, Bovine / metabolism
  • Shewanella / chemistry*
  • Spectrometry, Mass, Electrospray Ionization / instrumentation*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Trypsin / metabolism

Substances

  • Bacterial Proteins
  • Proteome
  • Serum Albumin, Bovine
  • Trypsin