Dataset Information

Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication.

ABSTRACT:

Background

Mitochondria are highly complex, membrane-enclosed organelles that are essential to the eukaryotic cell. The experimental elucidation of organellar proteomes combined with the sequencing of complete genomes allows us to trace the evolution of the mitochondrial proteome.

Results

We present a systematic analysis of the evolution of mitochondria via gene duplication in the human lineage. The most common duplications are intra-mitochondrial, in which the ancestral gene and the daughter genes encode mitochondrial proteins. These duplications significantly expanded carbohydrate metabolism, the protein import machinery and the calcium regulation of mitochondrial activity. The second most prevalent duplication, inter-compartmental, extended the catalytic as well as the RNA processing repertoire by the novel mitochondrial localization of the protein encoded by one of the daughter genes. Evaluation of the phylogenetic distribution of N-terminal targeting signals suggests a prompt gain of the novel localization after inter-compartmental duplication. Relocalized duplicates are more often expressed in a tissue-specific manner relative to intra-mitochondrial duplicates and mitochondrial proteins in general. In a number of cases, inter-compartmental duplications can be observed in parallel in yeast and human lineages leading to the convergent evolution of subcellular compartments.

Conclusions

One-to-one human-yeast orthologs are typically restricted to their ancestral subcellular localization. Gene duplication relaxes this constraint on the cellular location, allowing nascent proteins to be relocalized to other compartments. We estimate that the mitochondrial proteome expanded at least 50% since the common ancestor of human and yeast.

SUBMITTER: Szklarczyk R

PROVIDER: S-EPMC3091328 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication.

Szklarczyk Radek R Huynen Martijn A MA

Genome biology 20091124 11

<h4>Background</h4>Mitochondria are highly complex, membrane-enclosed organelles that are essential to the eukaryotic cell. The experimental elucidation of organellar proteomes combined with the sequencing of complete genomes allows us to trace the evolution of the mitochondrial proteome.<h4>Results</h4>We present a systematic analysis of the evolution of mitochondria via gene duplication in the human lineage. The most common duplications are intra-mitochondrial, in which the ancestral gene and ...[more]

PMID: 19930686

Similar Datasets

Project description:Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle whereas a significant fraction may reside elsewhere. As a step toward a comprehensive cellular map, we used subcellular fractionation with classic balance sheet analysis and isobaric labeling/quantitative mass spectrometry to assign locations to >6000 rat liver proteins. We provide quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments: nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, Golgi, plasma membrane and cytosol. Accounting for total intracellular distribution improves quality of organelle assignments and assigns proteins with multiple locations. Protein assignments and supporting data are available online through the Prolocate website (http://prolocate.cabm.rutgers.edu). As an example of the utility of this data set, we have used organelle assignments to help analyze whole exome sequencing data from an infant dying at 6 months of age from a suspected neurodegenerative lysosomal storage disorder of unknown etiology. Sequencing data was prioritized using lists of lysosomal proteins comprising well-established residents of this organelle as well as novel candidates identified in this study. The latter included copper transporter 1, encoded by SLC31A1, which we localized to both the plasma membrane and lysosome. The patient harbors two predicted loss of function mutations in SLC31A1, suggesting that this may represent a heretofore undescribed recessive lysosomal storage disease gene.

Project description:BACKGROUND:Protein-protein interactions are crucial for normal biological processes and to regulate cellular reactions that affect gene expression and function. Several previous studies have emphasized the roles of residues at the interface of protein-protein complexes in conferring stability and specificity to the complex. Interface residues in a protein are well known for their interactions with sidechain and main chain atoms with the interacting protein. However, the extent of intra-protein interactions involving interface residues in a protein-protein complex and their relative contribution in comparison to inter-protein interactions are not clearly understood. This paper probes this feature using a dataset of protein-protein complexes of known 3-D structure. RESULTS:We have analysed a dataset of 45 transient protein-protein complex structures with at least one of the interacting proteins with a known structure available also in the unbound form. We observe that a large proportion of interface residues (1608 out of 2137 interface residues, 75%) are involved in intra and inter-protein interactions simultaneously. The amino acid propensities of such interfacial residues involved in bifurcated interactions are found to be highly similar to the general propensities to occur at protein-protein interfaces. Finally, we observe that a majority (83%) of intra-protein interactions of interface residues with bifurcated interactions, are also observed in the protein uncomplexed form. CONCLUSIONS:We have shown, to the best of our knowledge for the first time, that a vast majority of the protein-protein interface residues are involved in extensive intra-protein interactions apart from inter-protein interactions. For a majority of such interface residues the microenvironment in the tertiary structure is pre-formed and retained upon complex formation with its cognate partner during transient interactions. REVIEWERS:This article was reviewed by Arumay Pal and Mallur Madhusudhan.

Dataset Information

Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication.

Background

Results

Conclusions

Publications

Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets