| Structural highlights
Function
[TIM13_YEAST] Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIM8-TIM13 complex is non essential and only mediates the import of few proteins under precise conditions while the predominant TIM9-TIM10 70 kDa complex is crucial and mediates the import of much more proteins. Strictly required for import of TIM23 in some conditions, when a low membrane potential exists in the mitochondria.[1] [2] [3] [4] [5] [TIM8_YEAST] Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIM8-TIM13 complex is non essential and only mediates the import of few proteins under precise conditions, while the predominant TIM9-TIM10 70 kDa complex is crucial and mediates the import of much more proteins. Strictly required for import of TIM23 in some conditions, when a low membrane potential exists in the mitochondria.[6] [7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Tim8-Tim13 complex, located in the mitochondrial intermembrane space, functions in the TIM22 import pathway that mediates the import of the mitochondrial carriers Tim23, Tim22, and Tim17 into the mitochondrial inner membrane. The Tim8-Tim13 complex assembles as a hexamer and binds to the substrate Tim23 to chaperone the hydrophobic Tim23 across the aqueous intermembrane space. However, both structural features of the Tim8-Tim13 complex and the binding interaction to Tim23 remain poorly defined. The crystal structure of the yeast Tim8-Tim13 complex, reported here at 2.6 A resolution, reveals that the architecture of the Tim8-Tim13 complex is similar to those of other chaperones such as Tim9-Tim10, prefoldin, and Skp, in which long helices extend from a central body like tentacles from a jellyfish. Surface plasmon resonance was applied to investigate interactions between the Tim8-Tim13 complex and Tim23. The Tim8-Tim13 complex contained approximately six binding sites and showed a complex binding interaction indicative of positive cooperativity rather than a simple bimolecular interaction. By combining results from the structural and binding studies, we provide a molecular model of the Tim8-Tim13 complex binding to Tim23. The regions where the tentacle helices attach to the body of the Tim8-Tim13 complex contain six hydrophobic pockets that likely interact with specific sequences of Tim23 and possibly other substrates. Smaller hydrophobic patches on the tentacles themselves likely interact nonspecifically with the substrate's transmembrane helices, shielding it from the aqueous intermembrane space. The central region of Tim23, which enters the intermembrane space first, may serve to nucleate the binding of the Tim8-Tim13 complex, thereby initiating the chaperoned translocation of Tim23 to the mitochondrial inner membrane.
The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23.,Beverly KN, Sawaya MR, Schmid E, Koehler CM J Mol Biol. 2008 Oct 24;382(5):1144-56. Epub 2008 Jul 30. PMID:18706423[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Leuenberger D, Bally NA, Schatz G, Koehler CM. Different import pathways through the mitochondrial intermembrane space for inner membrane proteins. EMBO J. 1999 Sep 1;18(17):4816-22. PMID:10469659 doi:http://dx.doi.org/10.1093/emboj/18.17.4816
- ↑ Paschen SA, Rothbauer U, Kaldi K, Bauer MF, Neupert W, Brunner M. The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J. 2000 Dec 1;19(23):6392-400. PMID:11101512 doi:http://dx.doi.org/10.1093/emboj/19.23.6392
- ↑ Davis AJ, Sepuri NB, Holder J, Johnson AE, Jensen RE. Two intermembrane space TIM complexes interact with different domains of Tim23p during its import into mitochondria. J Cell Biol. 2000 Sep 18;150(6):1271-82. PMID:10995434
- ↑ Murphy MP, Leuenberger D, Curran SP, Oppliger W, Koehler CM. The essential function of the small Tim proteins in the TIM22 import pathway does not depend on formation of the soluble 70-kilodalton complex. Mol Cell Biol. 2001 Sep;21(18):6132-8. PMID:11509656
- ↑ Curran SP, Leuenberger D, Schmidt E, Koehler CM. The role of the Tim8p-Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins. J Cell Biol. 2002 Sep 16;158(6):1017-27. Epub 2002 Sep 9. PMID:12221072 doi:http://dx.doi.org/10.1083/jcb.200205124
- ↑ Leuenberger D, Bally NA, Schatz G, Koehler CM. Different import pathways through the mitochondrial intermembrane space for inner membrane proteins. EMBO J. 1999 Sep 1;18(17):4816-22. PMID:10469659 doi:http://dx.doi.org/10.1093/emboj/18.17.4816
- ↑ Paschen SA, Rothbauer U, Kaldi K, Bauer MF, Neupert W, Brunner M. The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J. 2000 Dec 1;19(23):6392-400. PMID:11101512 doi:http://dx.doi.org/10.1093/emboj/19.23.6392
- ↑ Davis AJ, Sepuri NB, Holder J, Johnson AE, Jensen RE. Two intermembrane space TIM complexes interact with different domains of Tim23p during its import into mitochondria. J Cell Biol. 2000 Sep 18;150(6):1271-82. PMID:10995434
- ↑ Murphy MP, Leuenberger D, Curran SP, Oppliger W, Koehler CM. The essential function of the small Tim proteins in the TIM22 import pathway does not depend on formation of the soluble 70-kilodalton complex. Mol Cell Biol. 2001 Sep;21(18):6132-8. PMID:11509656
- ↑ Curran SP, Leuenberger D, Schmidt E, Koehler CM. The role of the Tim8p-Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins. J Cell Biol. 2002 Sep 16;158(6):1017-27. Epub 2002 Sep 9. PMID:12221072 doi:http://dx.doi.org/10.1083/jcb.200205124
- ↑ Beverly KN, Sawaya MR, Schmid E, Koehler CM. The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23. J Mol Biol. 2008 Oct 24;382(5):1144-56. Epub 2008 Jul 30. PMID:18706423 doi:10.1016/j.jmb.2008.07.069
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