Sequence-Based Prediction of Protein Solubility

Federico, Antonella; Vendruscolo, Michele; Tartaglia, Gian Gaetano

doi:10.1016/j.jmb.2011.12.005

Cited by 95 publications

(78 citation statements)

References 33 publications

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“…Our performances are comparable to other algorithms that were built to predict specific protein features. In agreement with previous observations, we found that physicochemical propensities linked to structural disorder and are relevant for RNA-binding, chaperone requirement and solubility (Agostini et al , 2012; Calloni et al , 2012; Cirillo et al , 2014), which very well captures the central role of natively unfolded proteins in higher eukaryotes (Babu et al , 2011). This observation is further supported by direct comparison of H.sapiens and E.coli proteomes, which shows enrichment in hydrophobicity and aggregation propensity for E.coli and structural disorder for H.sapiens (all links to results are provided in Supplementary Table S1).…”

Section: Discussionsupporting

confidence: 92%

“…To build a predictor of protein solubility, we took advantage of a study in which the solubility of 70% of Escherichia coli proteins was experimentally measured using an in vivo translation system (Niwa et al , 2009). In this analysis, we ranked proteins by their solubility and used top (1000 soluble proteins) and bottom (1000 insoluble proteins) elements as the positive and negative sets (Agostini et al , 2012). …”

Section: Resultsmentioning

confidence: 99%

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The cleverSuite approach for protein characterization: predictions of structural properties, solubility, chaperone requirements and RNA-binding abilities

et al. 2014

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Motivation: The recent shift towards high-throughput screening is posing new challenges for the interpretation of experimental results. Here we propose the cleverSuite approach for large-scale characterization of protein groups.Description: The central part of the cleverSuite is the cleverMachine (CM), an algorithm that performs statistics on protein sequences by comparing their physico-chemical propensities. The second element is called cleverClassifier and builds on top of the models generated by the CM to allow classification of new datasets.Results: We applied the cleverSuite to predict secondary structure properties, solubility, chaperone requirements and RNA-binding abilities. Using cross-validation and independent datasets, the cleverSuite reproduces experimental findings with great accuracy and provides models that can be used for future investigations.Availability: The intuitive interface for dataset exploration, analysis and prediction is available at http://s.tartaglialab.com/clever_suite.Contact: gian.tartaglia@crg.esSupplementary information: Supplementary data are available at Bioinformatics online.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

The cleverSuite approach for protein characterization: predictions of structural properties, solubility, chaperone requirements and RNA-binding abilities

et al. 2014

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“…It is intriguing to address whether inclusion bodies are amorphous aggregates or amyloid fibrils, or a mixture of the two (6,7). Recently, it has been suggested that the propensity for aggregation is correlated with the structural classification of proteins (8) and that the thermodynamic stability of the native states is closely linked with the kinetic barriers of aggregation (9). However, it is often difficult to distinguish between amyloid fibrils and amorphous aggregates even though the two are usually distinct in their morphologies (10), so they tend to be treated together in both experimental and theoretical studies.…”

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confidence: 99%

Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation

Yoshimura

Lin

Yagi

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

269

363

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Amyloid fibrils and amorphous aggregates are two types of aberrant aggregates associated with protein misfolding diseases. Although they differ in morphology, the two forms are often treated indiscriminately. β 2 -microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, forms amyloid fibrils or amorphous aggregates depending on the NaCl concentration at pH 2.5. We compared the kinetics of their formation, which was monitored by measuring thioflavin T fluorescence, light scattering, and 8-anilino-1-naphthalenesulfonate fluorescence. Thioflavin T fluorescence specifically monitors amyloid fibrillation, whereas light scattering and 8-anilino-1-naphthalenesulfonate fluorescence monitor both amyloid fibrillation and amorphous aggregation. The amyloid fibrils formed via a nucleation-dependent mechanism in a supersaturated solution, analogous to crystallization. The lag phase of fibrillation was reduced upon agitation with stirring or ultrasonic irradiation, and disappeared by seeding with preformed fibrils. In contrast, the glass-like amorphous aggregates formed rapidly without a lag phase. Neither agitation nor seeding accelerated the amorphous aggregation. Thus, by monitoring the kinetics, we can distinguish between crystal-like amyloid fibrils and glass-like amorphous aggregates. Solubility and supersaturation will be key factors for further understanding the aberrant aggregation of proteins.protein aggregation | metastability | glass transition | ultrasonication

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“…denaturation follows first-order kinetics), partly by a remarkable optimization of electrostatic interactions in the protein native state. Thus the consensus-based approach can be efficiently applied to improve protein stability and solubility in vitro and possibly in vivo, which are known to strongly depend on protein thermodynamic and kinetic stabilities [44][45][46]. Our approach may thus have application to different fields of protein biotechnology aimed to reduce the degradation and aggregation rates of protein-based pharmaceutical drugs [47] and also, possibly, in preparations for ERT.…”

Section: Discussionmentioning

confidence: 99%

The consensus-based approach for gene/enzyme replacement therapies and crystallization strategies: the case of human alanine–glyoxylate aminotransferase

Mesa‐Torres

Yunta

Fabelo-Rosa

et al. 2014

Biochemical Journal

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Protein stability is a fundamental issue in biomedical and biotechnological applications of proteins. Among these applications, gene- and enzyme-replacement strategies are promising approaches to treat inherited diseases that may benefit from protein engineering techniques, even though these beneficial effects have been largely unexplored. In the present study we apply a sequence-alignment statistics procedure (consensus-based approach) to improve the activity and stability of the human AGT (alanine-glyoxylate aminotransferase) protein, an enzyme which causes PH1 (primary hyperoxaluria type I) upon mutation. By combining only five consensus mutations, we obtain a variant (AGT-RHEAM) with largely enhanced in vitro thermal and kinetic stability, increased activity, and with no side effects on foldability and peroxisomal targeting in mammalian cells. The structure of AGT-RHEAM reveals changes at the dimer interface and improved electrostatic interactions responsible for increased kinetic stability. Consensus-based variants maintained the overall protein fold, crystallized more easily and improved the expression as soluble proteins in two different systems [AGT and CIPK24 (CBL-interacting serine/threonine-protein kinase) SOS2 (salt-overly-sensitive 2)]. Thus the consensus-based approach also emerges as a simple and generic strategy to increase the crystallization success for hard-to-get protein targets as well as to enhance protein stability and function for biomedical applications.

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Sequence-Based Prediction of Protein Solubility

Cited by 95 publications

References 33 publications

The cleverSuite approach for protein characterization: predictions of structural properties, solubility, chaperone requirements and RNA-binding abilities

The cleverSuite approach for protein characterization: predictions of structural properties, solubility, chaperone requirements and RNA-binding abilities

Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation

The consensus-based approach for gene/enzyme replacement therapies and crystallization strategies: the case of human alanine–glyoxylate aminotransferase

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