Prediction of Signal Peptides in Proteins from Malaria Parasites

Abstract

Signal peptides are N-terminal presequences responsible for targeting proteins to the endomembrane system, and subsequent subcellular or extracellular compartments, and consequently condition their proper function. The significance of signal peptides stimulates development of new computational methods for their detection. These methods employ learning systems trained on datasets comprising signal peptides from different types of proteins and taxonomic groups. As a result, the accuracy of predictions are high in the case of signal peptides that are well-represented in databases, but might be low in other, atypical cases. Such atypical signal peptides are present in proteins found in apicomplexan parasites, causative agents of malaria and toxoplasmosis. Apicomplexan proteins have a unique amino acid composition due to their AT-biased genomes. Therefore, we designed a new, more flexible and universal probabilistic model for recognition of atypical eukaryotic signal peptides. Our approach called signalHsmm includes knowledge about the structure of signal peptides and physicochemical properties of amino acids. It is able to recognize signal peptides from the malaria parasites and related species more accurately than popular programs. Moreover, it is still universal enough to provide prediction of other signal peptides on par with the best preforming predictors.

The Evolution Study Of 6-Cysteine Family Member Protein of Plasmodium sp. As a Potential Drug Candidate Against Malaria Infection

“…Therefore, MEGAX software was recognized P. malariae as the outgroup among P41 protein sequences [14]. Signal peptide consists of three main parts, which are: n-region, h-region, and cregion, which responsible for targeting proteins to the endomembrane system [23].…”

“…Targeting protein with a signal peptide region as a drug or vaccine candidate might influence protein targeting to various extracellular or subcellular compartments in the Plasmodial species [23]. On the other hand, the coiled-coil region known to induce the immune response and block critical functions in multiple pathogens, including plasmodium [24].…”

“…The domain analysis showed that all Plasmodium species have a signal peptide region and some of them (P. berghei, P. malariae, and P. vivax) have a coiled-coil region. Both of these domains could be used as a vaccine target similar to P41 protein [23], [24]. However, the coiled-coil region that was detected in P230 protein is smaller compared to P41 protein.…”

“…Domain prediction of P41protein by using InterPro.Domain analysis detects the presence of signal peptide and coiled-coil region that could be used as a vaccine target[23],[24]. Signal peptide region present in all plasmodial species while the coiled-coil region only present in P. knowlesi, P. malariae, P. ovale.…”

Scalable, FACS-Free Genome-Wide Phenotypic Screening

“…As SP processing is a major (but not the only) proteolytic maturation event, we decided to use SP prediction tools to derive an approximation of a mature human proteome. FASTA sequences of human proteins were downloaded from Uniprot (filters: evidence at protein level and reviewed) and used as input for SignalP 4.0 41 (via SecretSanta 42 ), signalHSMM 43 and Phobius 44 . All tools were run from within R. The following parameters were used for SignalP 4.0: version 4.1, organism 'euk', run_mode 'starter', sensitive TRUE.…”