BBB seminar: Peter Roepstorff

Peter Roepstorff
Head of the Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark; Professor II at PROBE, University of Bergen

The first annotation of the human genome placed the number of protein coding genes at approximately 30 000 - 40 000, i.e., only approximately twice as many as that of the fly or worm and five times that of yeast. This strongly implies that protein complexity and regulation in higher eukaryotes is governed by co- and post-translational modifications and splicing events. It is becoming increasing obvious in biological studies that numerous proteins and protein complexes are regulated by post-translational modifications. Several protein modifications have been documented and methods to systematically identify post-translational modifications during protein identification studies are being developed. We have initiated an approach, which we term Modification Specific Proteomics, for specific detection of various types of protein modifications in proteomics. The detection of PTM's is very challenging because these are often transient and highly heterogeneous in terms of modified site (e.g. phosphorylation) as well as the modifying group (e.g. glycosylation). Our concept is based on specific detection of PTM's in the 2D-gel, by specific "pull-out" of modified proteins/peptides, or by selective detection of the specific type of PTM in the mass spectrometer. It will be illustrated by our recent attempts to perform phospho- and glyco-specific proteomics. These two types of modifications are found in more that 50 % of all proteins in higher organisms. Due to their implications on protein structure and function, studies of biological phenomena must include detailed elucidation of the protein modifications on a level compatible with proteomics studies.