Flavors of protein disorder

Vučetić, Slobodan; Brown, Celeste J.; Dunker, A. Keith; Obradović, Zoran

doi:10.1002/prot.10437

Cited by 368 publications

(379 citation statements)

References 44 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: 75%

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: 75%

Molecular Epitopes of the Ankyrin−Spectrin Interaction

et al. 2008

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“…The set of disordered proteins (DIS152 ) was developed based on the 145 disordered proteins used in our previous work 20 . This set was cleaned up by removing several incorrectly labeled chains as well as by adjusting order/disorder boundaries in a few others.…”

Section: Datasetsmentioning

confidence: 99%

“…In a previous study 20 , disorder predictors were built using ordinaryleast-squares (OLS) regression, logistic regression (LR), and neural networks (NN). A surprising result, but consistent with previous experience in protein secondary structur e prediction, was the relatively small difference between accuracies of linear predictors and neural networks.…”

Section: Pondr Vl3mentioning

confidence: 99%

“…In this way, information from neighboring positions is used to smooth out predictions and thus improve accuracy by removing occasional misclassifications. The moving-average approach simply averages the raw predictions across neighboring positions 20,38 . Another approach trains a second-stage neural network to map the raw predictions across neighboring residues to the final prediction for the current position 25,39 .…”

Section: Pondr Vl3mentioning

confidence: 99%

“…PONDR VLXT 18 , whose accuracy reached 70%, integrated three feed-forward neural network predictors: VL1 18 trained on 25 variously characterized disordered proteins with 64% prediction accuracy, XN and XC 19 trained on N-and C-terminal disordered residues respectively. PONDR VL2 20 was a linear predictor built using ordinary-least-squares (OLS) regression on a much larger set of 145 disordered proteins and 130 completely ordered proteins. Its prediction accuracies were 73% on disordered residues and 88% on ordered residues.…”

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.

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468

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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Prediction of Protein‐Protein Interactions from Evolutionary Information

Valencia

Pazos

2003

Structural Bioinformatics

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Flavors of protein disorder

Cited by 368 publications

References 44 publications

Molecular Epitopes of the Ankyrin−Spectrin Interaction

Molecular Epitopes of the Ankyrin−Spectrin Interaction

Optimizing Long Intrinsic Disorder Predictors With Protein Evolutionary Information

Prediction of Protein‐Protein Interactions from Evolutionary Information

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