Identifying disordered regions in proteins from amino acid sequence

Romero, Pedro; Obradović, Zoran; Kissinger, Charles R.; Villafranca, J. E.; Dunker, A. Keith

doi:10.1109/icnn.1997.611643

Cited by 221 publications

(293 citation statements)

References 11 publications

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“…4) and from modeling of their sequences (Supplemental Fig. S1) with disordered sequence predictors disEMBL (63), GlobPlot (64), PONDR (65,66), and DISOPRED2 (67). As noted in the RESULTS, the predicted presence of some of the intrinsically unstructured sequences of 272 and Zu5 in their parent spectrin binding domain attests to the context independence of this predicted disorder.…”

Section: Both Zu5 and 272 And Their Parent Spectrin Binding Domain Ofmentioning

confidence: 96%

Molecular Epitopes of the Ankyrin−Spectrin Interaction

et al. 2008

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Isoforms of ankyrin and its binding partner spectrin are responsible for a number of interactions in a variety of human cells. Conflicting evidence, however, had identified two different, non-overlapping human erythroid ankyrin subdomains, Zu5 and 272, as the minimum binding region for β-spectrin. Complementary studies on the ankyrin-binding domain of spectrin have been somewhat more conclusive yet have not presented binding in terms of well-phased, integral numbers of spectrin repeats. Thus, the objective of this study was to clearly define and characterize the minimal ankyrin−spectrin binding epitopes. Circular dichroism (CD) wavelength spectra of the aforementioned ankyrin subdomains show that these fragments are 30−60% unstructured. In contrast, human erythroid β-spectrin repeats 13, 14, 15, and 16 (prepared in all combinations of two adjacent repeats) demonstrated proper folding and stability as determined by CD and tryptophan wavelength and heat denaturation scans. Native polyacrylamide gel electrophoresis (PAGE) gel shifts as well as affinity pull-down assays implicated Zu5 and β-spectrin repeats 14−15 as the minimum binding epitopes. These results were confirmed by analytical ultracentrifugation to sedimentation equilibrium by which a 1:1 complex was obtained if and only if Zu5 was mixed with β-spectrin constructs containing repeats 14 and 15 in tandem. Surface plasmon resonance yielded a K D of 15.2 nM for binding of β-spectrin fragments to the ankyrin subdomain Zu5, accounting for all of the binding observed between the intact molecules. Collectively, these results show the 14th and 15th β-spectrin repeats comprise the minimal, phased region of β-spectrin, which binds ankyrin at the Zu5 subdomain with high affinity.

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Section: Both Zu5 and 272 And Their Parent Spectrin Binding Domain Ofmentioning

confidence: 96%

Molecular Epitopes of the Ankyrin−Spectrin Interaction

et al. 2008

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“…Over the last several years we and others have been developing predictors of natural disordered regions from amino acid sequence 17,19,20,[22][23][24][25][26][27] . Indeed, prediction of disorder was added to the Critical Assessment of Protein Structure prediction in the 2002 cycle (CASP5) 50 .…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we used the moving-average approach since it proved effective and efficient in our previous studies 17,18,20 . With this approach, the final prediction zi for position i is calculated as,…”

Section: Pondr Vl3mentioning

confidence: 99%

“…To test this hypothesis, disordered proteins characterized by various methods as well as completely ordered proteins were collected by literature and database searches, and our first Predictor Of Natural Disordered R egions (PONDR) called XL1 was built from these data to predict disordered regions based solely on the amino acid sequences . Using only 7 X-ray characterized partially disordered proteins , XL1 achieved 58% prediction accuracy 17 . Since this initial work, a series of PONDRs have been built and the overall prediction accuracy has been boosted to more than 80%.…”

Section: Introductionmentioning

confidence: 99%

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Optimizing Long Intrinsic Disorder Predictors With Protein Evolutionary Information

Peng

Vučetić

Radivojac

et al. 2005

J. Bioinform. Comput. Biol.

472

428

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Protein existing as an ensemble of structures, called intrinsically disordered, has been shown to be res ponsible for a wide variety of biological functions and to be common in nature. Here we focus on improving sequence-based predictions of long (> 30 amino acid residues) regions lacking specific 3-D structure by means of four new neural -network-based Predictors Of Natural Disordered Regions (PONDRs): VL3, VL3H, VL3P, and VL3E. PONDR VL3 used several features from a previously introduced PONDR VL2, but benefitted from optimized predictor models and a slightly larger (152 versus 145) set of disordered proteins that were cleaned of mislabeling errors found in the smaller set. PONDR VL3H utilized homologues of the disordered proteins in the training stage, while PONDR VL3P used attributes derived from sequence profiles obtained by PSI-BLAST searches. The measure of accuracy was the average between accuracies on disordered and ordered protein regions. By this measure, the 30-fold cross-validation accuracies of VL3, VL3H, and VL3P were, respectively, 83.6±1.4%, 85.3±1.4%, and 85.2±1.5%. By combining VL3H and VL3P, t he resulting PONDR VL3E achieved an accuracy of 86.7±1.4%. This is a significant improvement over our previous PONDRs VLXT (71.6±1.3%) and VL2 (80.9±1.4% ). The new disorder predictors with the corresponding datasets are freely accessible through the web server at www.ist.temple.edu/disprot.

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“…Numerous other predictors of intrinsic disorder were developed using various computational approaches, including analytical algebraic functions, linear least squares, logistic regression, neural networks, and support vector machines. 14,32,33,36,[38][39][40][41][42][43][44][45][46][47][48][49] There exist many methodologies for classifying proteins and protein regions into domains and families based on their amino acid sequences. 50-54 With the advent of bioinformatics techniques, many databases of protein families have been developed.…”

Section: Introductionmentioning

confidence: 99%

Conservation of Intrinsic Disorder in Protein Domains and Families: I. A Database of Conserved Predicted Disordered Regions

et al. 2006

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Many protein regions have been shown to be intrinsically disordered, lacking unique structure under physiological conditions. These intrinsically disordered regions are not only very common in proteomes, they are also crucial to the function of many proteins, especially those involved in signaling, recognition, and regulation. The goal of this work was to identify the prevalence, characteristics, and functions of conserved disordered regions within protein domains and families.A database was created to store the amino acid sequences of nearly one million proteins and their domain matches from the InterPro database, a resource integrating eight different protein family and domain databases. Disorder prediction was performed on these protein sequences. Regions of sequence corresponding to domains were aligned using a multiple sequence alignment tool. From this initial information, regions of conserved predicted disorder were found within the domains. The methodology for this search consisted of finding regions of consecutive positions in the multiple sequence alignments in which a 90% or more of the sequences were predicted to be disordered. This procedure was constrained to find such regions of conserved disorder prediction that were at least 20 amino acids in length.The results of this work were 3,653 regions of conserved disorder prediction, found within 2,898 distinct InterPro entries. Most regions of conserved predicted disorder detected were short, with less than 10% of those found exceeding 30 residues in length.

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Identifying disordered regions in proteins from amino acid sequence

Cited by 221 publications

References 11 publications

Molecular Epitopes of the Ankyrin−Spectrin Interaction

Molecular Epitopes of the Ankyrin−Spectrin Interaction

Optimizing Long Intrinsic Disorder Predictors With Protein Evolutionary Information

Conservation of Intrinsic Disorder in Protein Domains and Families: I. A Database of Conserved Predicted Disordered Regions

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