Computer-based prediction of mitochondria-targeting peptides.

Computational methods are invaluable when protein sequences, directly derived from genomic data, need functional and structural annotation. Subcellular localization is a feature necessary for understanding the protein role and the compartment where the mature protein is active and very difficult to characterize experimentally. Mitochondrial proteins encoded on the cytosolic ribosomes carry specific patterns in the precursor sequence from where it is possible to recognize a peptide targeting the protein to its final destination. Here we discuss to which extent it is feasible to develop computational methods for detecting mitochondrial targeting peptides in the precursor sequences and benchmark our and other methods on the human mitochondrial proteins endowed with experimentally characterized targeting peptides. Furthermore, we illustrate our newly implemented web server and its usage on the whole human proteome in order to infer mitochondrial targeting peptides, their cleavage sites, and whether the targeting peptide regions contain or not arginine-rich recurrent motifs. By this, we add some other 2,800 human proteins to the 124 ones already experimentally annotated with a mitochondrial targeting peptide.

[1]  P Vincens,et al.  Computational method to predict mitochondrially imported proteins and their targeting sequences. , 1996, European journal of biochemistry.

[2]  Satoru Miyano,et al.  Extensive feature detection of N-terminal protein sorting signals , 2002, Bioinform..

[3]  F. Legeai,et al.  Predotar: A tool for rapidly screening proteomes for N‐terminal targeting sequences , 2004, Proteomics.

[4]  G. Crooks,et al.  WebLogo: a sequence logo generator. , 2004, Genome research.

[5]  Stavros J. Hamodrakas,et al.  PredSL: A Tool for the N-terminal Sequence-based Prediction of Protein Subcellular Localization , 2006, Genom. Proteom. Bioinform..

[6]  Piero Fariselli,et al.  BaCelLo: a balanced subcellular localization predictor , 2006, ISMB.

[7]  J. N. Spelbrink,et al.  The mitochondria of cultured mammalian cells: II. Expression and visualization of exogenous proteins in fixed and live cells. , 2007, Methods in molecular biology.

[8]  S. Brunak,et al.  Locating proteins in the cell using TargetP, SignalP and related tools , 2007, Nature Protocols.

[9]  S. Carr,et al.  A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology , 2008, Cell.

[10]  N. Pfanner,et al.  The Mitochondrial Proteome: From Inventory to Function , 2008, Cell.

[11]  Piero Fariselli,et al.  Grammatical-Restrained Hidden Conditional Random Fields for Bioinformatics applications , 2009, Algorithms for Molecular Biology.

[12]  N. Pfanner,et al.  Mitochondrial protein import: from proteomics to functional mechanisms , 2010, Nature Reviews Molecular Cell Biology.

[13]  C. Meisinger,et al.  Processing of mitochondrial presequences. , 2012, Biochimica et biophysica acta.

[14]  Alan J. Robinson,et al.  MitoMiner: a data warehouse for mitochondrial proteomics data , 2011, Nucleic Acids Res..

[15]  Piero Fariselli,et al.  The prediction of organelle-targeting peptides in eukaryotic proteins with Grammatical-Restrained Hidden Conditional Random Fields , 2013, Bioinform..

[16]  María Martín,et al.  Activities at the Universal Protein Resource (UniProt) , 2013, Nucleic Acids Res..