Large-scale Mapping of Human Protein-Protein Interactions by Mass Spectrometry

Mol Syst Biol. 2007;3:89. doi: 10.1038/msb4100134. Epub 2007 Mar 13.

Abstract

Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunoprecipitation
  • Protein Binding
  • Proteins / metabolism*
  • Spectrometry, Mass, Electrospray Ionization / methods*

Substances

  • Proteins