From Protein Structure to Function with Bioinformatics.pdf

Chapter 5Bioinformatics Approaches to the Structureand Function of IntrinsicallyDisordered ProteinsPeter TompaAbstract Intrinsically disordered proteins (IDPs) exist and function without welldefined structures, which demands the structure-function paradigm be reassessed.Evidence is mounting that they carry out important functions in signal transductionand regulation of transcription, primarily in eukaryotes. By a battery of biophysicaltechniques, the structural disorder of about 500 proteins has been demonstrated,and functional studies have provided the basis of classifying their functions intovarious schemes. Indirect evidence suggests that the occurrence of disorder is widespread,and several thousand proteins with significant disorder exist in the humanproteome alone. To narrow the wide gap between known and anticipated IDPs, arange of bioinformatics algorithms have been developed, which can reliably predictthe disordered state from amino acid sequence. Attempts have also been made topredict IDP functions, although with much less success. Due to their fast evolution,and reliance on short motifs for function, sequence clues for recognizing IDPfunctions are rather limited. In this chapter we give a brief survey of the IDP field,with particular focus on their functions and bioinformatics approaches developedfor predicting their structure and function. Potential future directions of researchare also suggested and discussed.5.1 The Concept of Protein DisorderThe basic insight provided by the classical paradigm, which equated protein functionwith a stable 3D structure, had tremendous success in interpreting the function ofenzymes, receptors and structural proteins. Decades of structure determinationefforts and recent structural genomics programs have yielded 50,000 well-definedstructures deposited in the protein data bank (PDB, www.pdb.org), strongly reinforcingthe traditional view. The recent recognition that many proteins or regions ofP. TompaInstitute of Enzymology, Biological Research Center, Hungarian Academy of Sciences,1518 Budapest, Hungarye-mail: tompa@enzim.huD.J. Rigden (ed.) From Protein Structure to Function with Bioinformatics, 113© Springer Science + Business Media B.V. 2009