[Frontiers in Bioscience 16, 1261-1275, January 1, 2011]

From sequence to structural analysis in protein phosphorylation motifs

Allegra Via1, Francesca Diella2, 3, Toby James Gibson2, Manuela Helmer-Citterich4

1Biocomputing group, Department of Biochemical Science "A. Rossi Fanelli", Sapienza University of Rome, P.le Aldo Moro 5, Rome, Italy, 2European Molecular Biology Laboratory, Postfach 10.2209, 69012 Heidelberg, Germany, 3Biobyte solutions GmbH, Boxbergring 16, 69126 Heidelberg, Germany,4Center for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Substrate specificity and phosphorylation linear motifs
4. Structural features of phosphorylation motifs
4.1. Can phosphorylation 3D motifs be defined?
4.2. Characterizing the P-site 3D environment (or signature motifs)
4.3. Structural features identified in systematic structural analyses of phosphorylation sites
5. Structural information in phosphorylation site predictors
6. Conclusions
7. Acknowledgements
8. References

1. ABSTRACT

Phosphorylation is the most widely studied post-translational modification occurring in cells. While mass spectrometry-based proteomics experiments are uncovering thousands of novel in vivo phosphorylation sites, the identification of kinase specificity rules still remains a relatively slow and often inefficacious task. In the last twenty years, many efforts have being devoted to the experimental and computational identification of sequence and structural motifs encoding kinase-substrate interaction key residues and the phosphorylated amino acid itself. In this review, we retrace the road to the discovery of phosphorylation sequence motifs, examine the progresses achieved in the detection of three-dimensional motifs and discuss their importance in the understanding of regulation and de-regulation of many cellular processes.