Dual Targeted Mitochondrial Proteins Are Characterized by Lower MTS Parameters and Total Net Charge

Maya Dinur-Mills,Merav Tal,Ophry Pines,Richard R Copley

doi:10.1371/journal.pone.0002161

Abstract

BackgroundIn eukaryotic cells, identical proteins can be located in different subcellular compartments (termed dual-targeted proteins).Methodology/Principal FindingsWe divided a reference set of mitochondrial proteins (published single gene studies) into two groups: i) Dual targeted mitochondrial proteins and ii) Exclusive mitochondrial proteins. Mitochondrial proteins were considered dual-targeted if they were also found or predicted to be localized to the cytosol, the nucleus, the endoplasmic reticulum (ER) or the peroxisome. We found that dual localized mitochondrial proteins have i) A weaker mitochondrial targeting sequence (MitoProtII score, hydrophobic moment and number of basic residues) and ii) a lower whole-protein net charge, when compared to exclusive mitochondrial proteins. We have also generated an annotation list of dual-targeted proteins within the predicted yeast mitochondrial proteome. This considerably large group of dual-localized proteins comprises approximately one quarter of the predicted mitochondrial proteome. We supported this prediction by experimental verification of a subgroup of the predicted dual targeted proteins.Conclusions/SignificanceTaken together, these results establish dual targeting as a widely abundant phenomenon that should affect our concepts of gene expression and protein function. Possible relationships between the MTS/mature sequence traits and protein dual targeting are discussed.

Highlights

In certain cases, identical or almost identical proteins can be found in more than one compartment, giving rise to isoprotein distribution [1,2,3]
To identify putative mitochondrial proteins that may be located in a second subcellular location, we considered proteins as dual localized if they were found in a second location according genomic screens including green fluorescent protein (GFP) tagging, the TRIPLE database or bioinformatic predictions of targeting signals to the peroxisome and endoplasmic reticulum (ER) (Table 1)
This study shows that dual localized mitochondrial proteins are characterized by a lower probability of mitochondrial targeting (MitoProtII score) and weaker mitochondrial targeting sequence (MTS) parameters when compared to exclusive mitochondrial proteins

Summary

Introduction

Identical or almost identical proteins can be found in more than one compartment, giving rise to isoprotein distribution [1,2,3]. A number of mechanisms can generate dual distribution between subcellular compartments These mechanisms can be divided into two main groups based on the number of translation products that are generated. Isoprotein distribution due to two translation products can be achieved by several routes that are based on two genes, two mRNAs from a single gene or two translation initiations from a single mRNA. In all these cases the two isoproteins differ by the presence or absence of a targeting signal (reviewed in [1,3]). Identical proteins can be located in different subcellular compartments (termed dualtargeted proteins)

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Results

Conclusion