Effect of protein structure on mitochondrial import

Wilcox, Allen J.; Choy, Jason; Bustamante, Carlos; Matouschek, Andreas T

doi:10.1073/pnas.0507324102

Cited by 91 publications

(72 citation statements)

References 42 publications

(36 reference statements)

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“…Such a disordered motif has also been proposed for several other colicins, but it was only rarely determined because of the disorder of this part in the crystal lattices (1). Notably, the presence of an unstructured N-terminal sequence in proteins designed to unfold during translocation has also been observed for proteins destined to the mitochondrial matrix and to the proteasomal cavity (35). A high flexibility is probably the prerequisite as the N-terminal part of colicin M must interact with the periplasmically localized TonB protein (see also Fig.…”

Section: Structure Solution and Comparison Of Independent Modelsmentioning

confidence: 97%

Crystal Structure of Colicin M, a Novel Phosphatase Specifically Imported by Escherichia coli>

Zeth

Römer

Patzer

et al. 2008

Journal of Biological Chemistry

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Colicins are cytotoxic proteins secreted by certain strains of Escherichia coli. Colicin M is unique among these toxins in that it acts in the periplasm and specifically inhibits murein biosynthesis by hydrolyzing the pyrophosphate linkage between bactoprenol and the murein precursor. We crystallized colicin M and determined the structure at 1.7 Å resolution using x-ray crystallography. The protein has a novel structure composed of three domains with distinct functions. The N-domain is a short random coil and contains the exposed TonB box. The central domain includes a hydrophobic ␣-helix and binds presumably to the FhuA receptor. The C-domain is composed of a mixed ␣/␤-fold and forms the phosphatase. The architectures of the individual modules show no similarity to known structures. Amino acid replacements in previously isolated inactive colicin M mutants are located in the phosphatase domain, which contains a number of surface-exposed residues conserved in predicted bacteriocins of other bacteria. The novel phosphatase domain displays no sequence similarity to known phosphatases. The N-terminal and central domains are not conserved among bacteriocins, which likely reflect the distinct import proteins required for the uptake of the various bacteriocins. The homology pattern supports our previous proposal that colicins evolved by combination of distinct functional domains.Colicins are plasmid-encoded toxic proteins produced by Escherichia coli to kill E. coli strains that lack the respective colicin-encoding plasmid (1). Approximately half of the natural E. coli isolates produce one or more of these toxins. Colicins either specifically cleave DNA, rRNA, tRNA or form pores in the cytoplasmic membrane, thereby dissipating the electrochemical potential.Colicins are not translocated uni-directionally like most other translocated bacterial proteins, i.e. from the cytoplasm to the cytoplasmic membrane, the periplasm, the outer membrane, and the environment of the cell, but are rather translocated in both directions, i.e. released by the producer cells and imported by colicin-sensitive cells. The mechanism of colicin import is highly specific and involves cognate outer membrane receptor proteins and an energy-coupled transport across the outer membrane. Energy driving the import across the outer membrane is provided by the proton motive force across the cytoplasmic membrane. Energy coupling between the outer and cytoplasmic membranes is mediated by either the Ton system or the Tol system. The Ton system consists of the three membrane proteins TonB, ExbB, and ExbD.Colicin M belongs to the group of colicins whose uptake requires the Ton system (2, 3). These colicins contain a consensus sequence of seven residues at the N terminus, designated as the TonB box, which is also present in all outer membrane transport proteins that require the Ton system and the proton motive force for the import of substrates (4, 5). Both colicin M and its receptor FhuA contain the TonB box, and both are required for the import of colicin M (6...

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Section: Structure Solution and Comparison Of Independent Modelsmentioning

confidence: 97%

Crystal Structure of Colicin M, a Novel Phosphatase Specifically Imported by Escherichia coli>

Zeth

Römer

Patzer

et al. 2008

Journal of Biological Chemistry

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“…The development of longer targeting sequences allowed for an increased pulling force to enable unfolding of folded domains [40] and to sort some proteins into the intermembrane space by a stop-transfer mechanism [32], where processing the various stop-transfer substrates relies on a heteromeric IMP complex. Trypanosoma brucei might have been denied these developments and, consequently, this would constrain the protein substrates able to be imported into the mitochondrion.…”

Section: The Protein Import Machinery In Trypanosoma Bruceimentioning

confidence: 99%

The direct route: a simplified pathway for protein import into the mitochondrion of trypanosomes

Schneider

Bursać

Lithgow

2008

Trends in Cell Biology

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“…Each mitochondrion contains 2-10 copies of a circular genome that codes for 13 proteins, 22 tRNAs, and 2 rRNAs (2). The balance of the proteins that are incorporated into mitochondria are coded by the nuclear genome and then incorporated via the mitochondrial import apparatus in a distribution that is specific to the tissue in which the mitochondria reside (3,21,23,33). This differential protein expression leads to mitochondria that are vastly different in their metabolic function and activity level between tissues.…”

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confidence: 99%

Tissue heterogeneity of the mammalian mitochondrial proteome

Johnson

Harris²,

French

et al. 2007

American Journal of Physiology-Cell Physiology

185

145

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functionality of the mitochondrion is primarily determined by nuclear encoded proteins. The mitochondrial functional requirements of different tissues vary from a significant biosynthetic role (liver) to a primarily energy metabolism-oriented organelle (heart). The purpose of this study was to compare the mitochondrial proteome from four different tissues of the rat, brain, liver, heart, and kidney, to provide insight into the extent of mitochondrial heterogeneity and to further characterize the overall mitochondrial proteome. Mitochondria were isolated, solubilized, digested, and subjected to quantitative liquid chromatography-mass spectroscopy. Of the 16,950 distinct peptides detected, 8,045 proteins were identified. High-confidence identification threshold was reached by 1,162 peptides, which were further analyzed. Of these 1,162 proteins, 1,149 were significantly different in content (P and q values Ͻ 0.05) between at least 2 tissues, whereas 13 were not significantly different between any tissues. Confirmation of the mitochondrial origin of proteins was determined from the literature or via NH2-terminal mitochondrial localization signals. With these criteria, 382 proteins in the significantly different groups were confirmed to be mitochondrial, and 493 could not be confirmed to be mitochondrial but were not definitively localized elsewhere in the cell. A total of 145 proteins were assigned to the rat mitochondrial proteome for the first time via their NH 2-terminal mitochondrial localization signals. Among the proteins that were not significantly different between tissues, three were confirmed to be mitochondrial. Most notable of the significantly different proteins were histone family proteins and several structural proteins, including tubulin and intermediate filaments. The mitochondrial proteome from each tissue had very specific characteristics indicative of different functional emphasis. These data confirm the notion that mitochondria are tuned by the nucleus for specific functions in different tissues. structural proteins; oxidative phosphorylation; liquid chromatography; mass spectrometry; electrophoresis; histone; liver; heart; kidney; brain MITOCHONDRIA ARE semi-self-replicating organelles responsible for several essential functions in mammalian cells, including oxidative phosphorylation, apoptosis, iron-sulfur cluster assembly, and several important catabolic pathways. Each mitochondrion contains 2-10 copies of a circular genome that codes for 13 proteins, 22 tRNAs, and 2 rRNAs (2). The balance of the proteins that are incorporated into mitochondria are coded by the nuclear genome and then incorporated via the mitochondrial import apparatus in a distribution that is specific to the tissue in which the mitochondria reside (3,21,23,33). This differential protein expression leads to mitochondria that are vastly different in their metabolic function and activity level between tissues. A scan of the human genome predicts as many as 3,000 proteins localized to the mitochondria (28, 32). The most current...

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Effect of protein structure on mitochondrial import

Cited by 91 publications

References 42 publications

Crystal Structure of Colicin M, a Novel Phosphatase Specifically Imported by Escherichia coli>

Crystal Structure of Colicin M, a Novel Phosphatase Specifically Imported by Escherichia coli>

The direct route: a simplified pathway for protein import into the mitochondrion of trypanosomes

Tissue heterogeneity of the mammalian mitochondrial proteome

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