Prediction of neddylation sites from protein sequences and sequence-derived properties.

Ahmet Sinan Yavuz,Namık Berk Sözer,Osman Uğur Sezerman

doi:10.1186/1471-2105-16-s18-s9

Ahmet Sinan Yavuz, Namık Berk Sözer + Show 1 more

Open Access

https://doi.org/10.1186/1471-2105-16-s18-s9

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Abstract

BackgroundNeddylation is a reversible post-translational modification that plays a vital role in maintaining cellular machinery. It is shown to affect localization, binding partners and structure of target proteins. Disruption of protein neddylation was observed in various diseases such as Alzheimer's and cancer. Therefore, understanding the neddylation mechanism and determining neddylation targets possibly bears a huge importance in further understanding the cellular processes. This study is the first attempt to predict neddylated sites from protein sequences by using several sequence and sequence-based structural features.ResultsWe have developed a neddylation site prediction method using a support vector machine based on various sequence properties, position-specific scoring matrices, and disorder. Using 21 amino acid long lysine-centred windows, our model was able to predict neddylation sites successfully, with an average 5-fold stratified cross validation performance of 0.91, 0.91, 0.75, 0.44, 0.95 for accuracy, specificity, sensitivity, Matthew's correlation coefficient and area under curve, respectively. Independent test set results validated the robustness of reported new method. Additionally, we observed that neddylation sites are commonly flexible and there is a significant positively charged amino acid presence in neddylation sites.ConclusionsIn this study, a neddylation site prediction method was developed for the first time in literature. Common characteristics of neddylation sites and their discriminative properties were explored for further in silico studies on neddylation. Lastly, up-to-date neddylation dataset was provided for researchers working on post-translational modifications in the accompanying supplementary material of this article.

Highlights

Neddylation is a reversible post-translational modification that plays a vital role in maintaining cellular machinery
Resembling SUMO and other ubiquitin-like modifiers (Ubls) proteins, NEDD8 is synthesized in an immature form and activated by the cleavage of extra amino acids located beyond Gly76 [2]
Fine-tuned Support vector machine (SVM) classification results indicated that the highest average area under receiver-operator-characteristic curve (AUC) was obtained at a window size of 21 (Figure 1a)

Summary

Introduction

Neddylation is a reversible post-translational modification that plays a vital role in maintaining cellular machinery. Post-translational modifications (PTMs) are crucial mechanisms in cellular regulation. Studying post-translational modifications provide details for intricacies of protein function and response to various external or internal stimuli. Neddylation is a highly dynamic and reversible posttranslational modification, in which NEDD8 protein is covalently attached to a target lysine residue. NEDD8 protein shows ~60% sequence identity with ubiquitin, and it is the most similar protein to ubiquitin among other ubiquitin-like modifiers (Ubls) [1]. In addition to sequence identity, NEDD8 conjugation pathway is similar to that of the ubiquitin. NEDD8 proteins can be removed by NEDD8 isopeptidases, making neddylation a dynamic and reversible process [2]

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