eNergiome and N-TerPred: novel tools to improve the prediction of plastidic and mitochondrial mature N-termini,

Abstract

International audienceProteins N-terminus and related modifications influence protein fate and half-life. The most frequent co-translational N-terminal protein modifications are linked to initial methionine excision and protein N-alpha-acetylation. Another modification occurring next to the protein N-term corresponds to the excision of the transit peptide of nuclear-encoded proteins targeted to the mitochondria and/or the plastids. Only few bioinformatics tools are currently available to predict mature proteins N-term such as TermiNator3 (processing and modifications at position 1-2) and TargetP/ChloroP/SignalP tools that provide transit-peptide length predictions and protein subcellular localization. Unfortunately, the reliability of these tools suffer minor inconsistencies to major defects especially for the transit-peptide length prediction with the TargetP suite.Here, we present a dedicated database (eNergiomeDB) which data were collected from large scale N-terminomics studies. Experimental data related to protein N-terminus status and mature N-terminal start positions are complemented with subcellular localization information. eNergiomeDB provides the largest manually validated training set with almost 250,000 mature experimental N-termini related to more than 6,000 distinct non-redundant proteins (2,538 from A. thaliana, 3507 from H. Sapiens). More than 175,000 validated N-terminus peptides (associated to 1,925 proteins) were used to improve the existing N-terminus prediction tools and to develop a new one.This newly developed N-terPred tool suite integrates a few new features including improved N-term acetylation prediction especially for NatC substrates, subcellular localization prediction based on protein primary sequence and reliable cleavage sites of plastid and/or mitochondrial transit peptide for the A. thaliana and human nuclear-encoded proteins. These newer functionalities and their possible use on alternative species will be presented