The Tom Core Complex

Ahting, Uwe; Thun, Clemens; Hegerl, R.; Typke, Dieter; Nargang, Frank E.; Neupert, Walter; Nußberger, Stephan

doi:10.1083/jcb.147.5.959

Cited by 196 publications

(131 citation statements)

References 60 publications

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“…In agreement with this view the cytosolic domain of Tom20 was found to interact with the cytosolic domains of Tom70 and Tom22 (10,26). The lack of interactions between the membrane-spanning domains of Tom20 and Tom70 and membrane-embedded elements of the TOM complex would also explain why Tom20 and Tom70 are only peripheral members of the TOM complex (27,28). We propose that the main function of the N-terminal signal-anchor domains of Tom20 and Tom70 is not in their recruitment to the TOM complex but rather to keep these proteins in the plane of the outer membrane so that they can collect precursor proteins at the whole mitochondrial surface.…”

Section: Discussionmentioning

confidence: 99%

Signal-Anchor Domains of Proteins of the Outer Membrane of Mitochondria

Waizenegger

Stan

Neupert

et al. 2003

Journal of Biological Chemistry

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We have studied the topogenesis of a class of mitochondrial outer membrane proteins that expose a hydrophilic domain to the cytosol and are anchored to the membrane by a single transmembrane domain in the N-terminal region. To determine the role of these latter sequences in the targeting and insertion of such proteins we took two approaches. First, a functional complementation assay was used to define the structural elements that together with the anchor domain make up the topogenic signal. Moderate hydrophobicity of the transmembrane domain was found to be the most important requirement. Variants with a scrambled sequence of the membrane-spanning segment were only partially functional suggesting that specificity in the amino acid sequence is also of considerable importance. A net positive charge at both flanking regions of the transmembrane domain contributes to the efficiency of targeting and membrane integration but is not an essential structural feature of this signal. Second, chimeras of Tom20, Tom70, and OM45 were generated that contained the cytosolic domain of Tom20 or Tom70 and the anchor domain of one of the other members of the class. These hybrid proteins were able to rescue the growth of cells lacking Tom20 or Tom70. Thus, anchor domains of outer membrane proteins are functionally interchangeable. They play only a minor role in the specific function of these proteins, but have a decisive role in topogenic signaling.The targeting of most mitochondrial preproteins is mediated by cleavable N-terminal extensions of about 20 -50 amino acid residues (the presequences or matrix-targeting signals), which are necessary and sufficient to direct them into the mitochondria (1, 2). Yet, all preproteins of the mitochondrial outer membrane are devoid of a typical N-terminal presequence. The targeting information is rather contained in the protein sequence itself.A special class of mitochondrial outer membrane proteins includes those containing a single transmembrane segment at their N-terminal. The three known members of this class are Tom20, Tom70, and OM45 ( Fig. 1) (3). These proteins are present in the outer membrane in an orientation, where the bulk of the polypeptide is exposed to the cytosol and only a small N-terminal segment crosses the outer membrane. They are called "signal-anchored" proteins since their TMD 1 together with its flanking regions serve both as an intracellular sorting signal and as an anchor to the membrane. Tom20 and Tom70 are examples of this class of proteins. They function as receptor proteins that mediate the import of preproteins. Tom20 is involved in the translocation of most protein precursors, in particular those with N-terminal targeting signals (4, 5), whereas Tom70 forms a binding site for a more restricted set of preproteins, most notably the mitochondrial carrier family (6 -8). OM45, another member of this class, is a very abundant protein in the yeast mitochondrial outer membrane whose function, however, is unknown (9).The contribution of the signal-anchor domain to the fun...

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Section: Discussionmentioning

confidence: 99%

Signal-Anchor Domains of Proteins of the Outer Membrane of Mitochondria

Waizenegger

Stan

Neupert

et al. 2003

Journal of Biological Chemistry

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“…The conditions during BNGE cause the Tom20 and Tom70 receptors of both the yeast and N. crassa TOM complexes to dissociate from the remaining components that constitute the TOM core complex (10,11,23). Both Tom6 and Tom7 comigrate with Tom22 and Tom40 demonstrating their firm association with the core complex (Fig.…”

Section: Tom6 and Tom7 In Neurospora Crassamentioning

confidence: 99%

“…OMV were solubilized with either digitonin, a detergent that is known to keep the TOM holo complex intact (20), or DDM, which results in the formation of the TOM core complex (11). Tom6 and Tom7 were precipitated with antibodies against Tom22 and Tom40 (Fig.…”

Section: Tom6 and Tom7 In Neurospora Crassamentioning

confidence: 99%

“…Another receptor that forms a binding site for a more restricted set of preproteins, most notably the mitochondrial carrier family, is Tom70 (8,9). These receptors are loosely attached to the other components of the TOM machinery that form the core complex (10,11). The subunits of the core complex (Tom40, Tom22, Tom7, Tom6, and Tom5) are embedded in the outer membrane and form the translocation pore (10,11).…”

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confidence: 99%

“…These receptors are loosely attached to the other components of the TOM machinery that form the core complex (10,11). The subunits of the core complex (Tom40, Tom22, Tom7, Tom6, and Tom5) are embedded in the outer membrane and form the translocation pore (10,11). Tom40 represents the major component of the translocation pore (12,13), whereas Tom22 and Tom5 probably transfer preproteins from the receptors to the pore (14,15).…”

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Assembly of Tom6 and Tom7 into the TOM Core Complex ofNeurospora crassa

Dembowski

Künkele

Nargang

et al. 2001

Journal of Biological Chemistry

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Translocation of preproteins across the mitochondrial outer membrane is mediated by the translocase of the outer mitochondrial membrane (TOM) complex. We report the molecular identification of Tom6 and Tom7, two small subunits of the TOM core complex in the fungus Neurospora crassa. Cross-linking experiments showed that both proteins were found to be in direct contact with the major component of the pore, Tom40. In addition, Tom6 was observed to interact with Tom22 in a manner that depends on the presence of preproteins in transit. Precursors of both proteins are able to insert into the outer membrane in vitro and are assembled into authentic TOM complexes. The insertion pathway of these proteins shares a common binding site with the general import pathway as the assembly of both Tom6 and Tom7 was competed by a matrix-destined precursor protein. This assembly was dependent on the integrity of receptor components of the TOM machinery and is highly specific as in vitro-synthesized yeast Tom6 was not assembled into N. crassa TOM complex. The targeting and assembly information within the Tom6 sequence was found to be located in the transmembrane segment and a flanking segment toward the N-terminal, cytosolic side. A hybrid protein composed of the C-terminal domain of yeast Tom6 and the cytosolic domain of N. crassa Tom6 was targeted to the mitochondria but was not taken up into TOM complexes. Thus, both segments are required for assembly into the TOM complex. A model for the topogenesis of the small Tom subunits is discussed.

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Protein Transport in and out of the Endoplasmic Reticulum

Rapoport

2010

The Harvey Lectues

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The Tom Core Complex

Cited by 196 publications

References 60 publications

Signal-Anchor Domains of Proteins of the Outer Membrane of Mitochondria

Signal-Anchor Domains of Proteins of the Outer Membrane of Mitochondria

Assembly of Tom6 and Tom7 into the TOM Core Complex ofNeurospora crassa

Protein Transport in and out of the Endoplasmic Reticulum

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