From Protein Structure to Function with Bioinformatics.pdf

5 Structure and Function of Intrinsically Disordered Proteins 1355.7 ConclusionsIn general, the prediction of function is probably more difficult than prediction ofstructure, because similar structures may carry out completely different functions(see also Chapter 6). This is particularly true for IDPs, for which structure correspondsnot simply to the lack of a well-defined 3D fold, but to an ensemble ofinterconverting conformational states of various transient, but function-related,short- and long-range structural elements. A range of bioinformatics predictors reliablypredict the disordered state from amino acid sequence, and can also detectstructural elements probably related to function with reasonable accuracy. Attemptsto predict the function of IDPs from sequence, however, lag far behind predictionof structure. In addition, success is limited by complicating factors such as rapidevolution and frequent sequence-independence of function. Given the functionalimportance of many IDPs, one may anticipate significant activity in this area in thenear future.ReferencesAshburner M, Ball CA, Blake JA, et al. (2000) Gene ontology: tool for the unification of biology.The Gene Ontology Consortium. Nat Genet 25:25–29Bell S, Klein C, Muller L, et al. (2002) p53 contains large unstructured regions in its native state.J Mol Biol 322:917–927Bhattacharyya RP, Remenyi A, Good MC, et al. (2006) The Ste5 scaffold allosterically modulatessignaling output of the yeast mating pathway. Science 311:822–826Blom N, Gammeltoft S, Brunak S (1999) Sequence and structure-based prediction of eukaryoticprotein phosphorylation sites. J Mol Biol 294:1351–1362Bordoli L, Kiefer F, Schwede T (2007) Assessment of disorder predictions in CASP7. Proteins69(Suppl 8):129–136Bourhis JM, Receveur-Brechot V, Oglesbee M, et al. (2005) The intrinsically disordered C-terminaldomain of the measles virus nucleoprotein interacts with the C-terminal domain of thephosphoprotein via two distinct sites and remains predominantly unfolded. Protein Sci14:1975–1992Brown CJ, Takayama S, Campen AM, et al. (2002) Evolutionary rate heterogeneity in proteinswith long disordered regions. J Mol Evol 55:104–110Bustos DM, Iglesias AA (2006) Intrinsic disorder is a key characteristic in partners that bind 14-3-3 proteins. Proteins: Struct, Funct, Bioinformatics 63:35–42Chen JW, Romero P, Uversky VN, et al. (2006a) Conservation of intrinsic disorder in proteindomains and families: I. A database of conserved predicted disordered regions. J Proteome Res5:879–887Chen JW, Romero P, Uversky VN, et al. (2006b) Conservation of intrinsic disorder in proteindomains and families: II. functions of conserved disorder. J Proteome Res 5:888–898Cheng Y, Oldfield CJ, Meng J, et al. (2007) Mining alpha-Helix-Forming MolecularRecognition Features with Cross Species Sequence Alignments. Biochemistry46:13468–13477Coeytaux K, Poupon A (2005) Prediction of unfolded segments in a protein sequence based onamino acid composition. Bioinformatics 21:1891–1900