Analysis of proteins and proteomes by mass spectrometry

A decade after the discovery of electrospray and matrix-assisted laser deso rption ionization (MALDI), methods that finally allowed gentle ionization o f large biomolecules, mass spectrometry has become a powerful tool in prote in analysis and the key technology in the emerging field of proteomics. The success of mass spectrometry is driven both by innovative instrumentation designs, especially those operating on the time-of-flight or ion-trapping p rinciples, and by large-scale biochemical strategies, which use mass spectr ometry to detect the isolated proteins. Any human protein can now be identi fied directly from genome databases on the basis of minimal data derived by mass spectrometry. As has already happened in genomics, increased automati on of sample handling, analysis, and the interpretation of results will gen erate an avalanche of qualitative and quantitative proteomic data. Protein- protein interactions can be analyzed directly by precipitation of a tagged bait followed by mass spectrometric identification of its binding partners. By these and similar strategies, entire protein complexes, signaling pathw ays, and whole organelles are being characterized. Posttranslational modifi cations remain difficult to analyze but are starting to yield to generic st rategies.