From Protein Structure to Function with Bioinformatics.pdf

5 Structure and Function of Intrinsically Disordered Proteins 123namely molecular function (MF), biological process (BP) and cellular localization(CL). In practically complete agreement, different works suggest agree that the frequencyof disorder is sharply higher in eukaryotes than in prokaryotes, and thatdisorder is common in regulatory and signalling functions. In terms of MF, the highestlevels of disorder appear in categories such as transcription regulation, proteinkinase, transcription factor, DNA binding, whereas it is lowest in oxidoreductase,catalytic, ligase, structural molecule categories. In terms of BP, categories such asdevelopment, protein phosphorylation, regulation of transcription, signal transductionhave the highest level of disorder, whereas in biosynthesis and energy pathways itappears infrequently. With respect to localization, it prevails in nuclear, cytoskeletaland chromosomal proteins, for example, with low levels in mitochondrial, cytoplasmicand membrane proteins.When prediction is focused on long disordered regions, thought to be functionallysignificant (Xie et al. 2007), similar observations have been made. When SwissProtBP key-words were analyzed, significant positive (e.g., differentiation, transcription,transcription regulation), and negative (e.g., biosynthesis, transport, electron transport,glycolysis) correlations with disorder were found (Xie et al. 2007). When MFkeywords were analyzed, most positively correlated were ribonucleoprotein, ribosomalprotein, developmental protein, whereas negatively correlated were oxidoreductase,transferase, lyase, hydrolase. In terms of 710 functional SwissProtkey-words, 238 were in strongly positive, whereas 302 in strongly negative, correlationwith disorder; 170 keywords were ambiguous.Taken together, all the pertinent studies agree that proteins of regulatory functionsare positively correlated with disorder, whereas proteins with catalytic functions arenegatively associated.5.4.2 Classification of IDPs Based on Their Mechanismof ActionIn another system taking the molecular mechanisms of IDPs into consideration,disordered proteins have been classified into five (Tompa 2002) and later into six(Tompa 2005) categories. Recent observations have suggested the addition of prionproteins as an additional category (Pierce et al. 2005). This classification scheme(Table 5.2) can accommodate all distinct modes of IDP/IDR actions described thusfar (Sickmeier et al. 2007).5.4.2.1 Entropic ChainsThe first functional category, unique to disordered proteins, is that of entropicchains, the function of which does not involve partner recognition, but directlyresults from disorder. Sub-categories within this class are termed entropic springs,