| Structural highlights
Function
TIM9_YEAST Mitochondrial intermembrane chaperone that participates in the import and insertion of 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. Compared to TIM10, it may have a strong structural role.[1] [2] [3] [4] [5] [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
Monitoring Editor: Thomas D. Fox The Tim9-Tim10 complex plays an essential role in mitochondrial protein import by chaperoning select hydrophobic precursor proteins across the intermembrane space. How the complex interacts with precursors is not clear, although it has been proposed that Tim10 acts in substrate recognition, while Tim9 acts in complex stabilization. In this study, we report the structure of the yeast Tim9-Tim10 hexameric assembly determined to 2.5 A and have performed mutational analysis in yeast to evaluate the specific roles of Tim9 and Tim10. Like the human counterparts, each Tim9 and Tim10 subunit contains a central loop flanked by disulfide bonds that separate two extended N- and C-terminal tentacle-like helices. Buried salt-bridges between highly conserved lysine and glutamate residues connect alternating subunits. Mutation of these residues destabilizes the complex, causes defective import of precursor substrates and results in yeast growth defects. Truncation analysis revealed that in the absence of the N-terminal region of Tim9, the hexameric complex is no longer able to efficiently trap incoming substrates even though contacts with Tim10 are still made. We conclude that Tim9 plays an important functional role that includes facilitating the initial steps in translocating precursor substrates into the intermembrane space.
Structural and Functional Requirements for Activity of the Tim9-Tim10 Complex in Mitochondrial Protein Import.,Baker MJ, Webb CT, Stroud DA, Palmer CS, Frazier AE, Guiard B, Chacinska A, Gulbis JM, Ryan MT Mol Biol Cell. 2008 Nov 26. PMID:19037098[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Endres M, Neupert W, Brunner M. Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex. EMBO J. 1999 Jun 15;18(12):3214-21. PMID:10369662 doi:http://dx.doi.org/10.1093/emboj/18.12.3214
- ↑ 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
- ↑ Luciano P, Vial S, Vergnolle MA, Dyall SD, Robinson DR, Tokatlidis K. Functional reconstitution of the import of the yeast ADP/ATP carrier mediated by the TIM10 complex. EMBO J. 2001 Aug 1;20(15):4099-106. PMID:11483513 doi:http://dx.doi.org/10.1093/emboj/20.15.4099
- ↑ 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
- ↑ Vial S, Lu H, Allen S, Savory P, Thornton D, Sheehan J, Tokatlidis K. Assembly of Tim9 and Tim10 into a functional chaperone. J Biol Chem. 2002 Sep 27;277(39):36100-8. Epub 2002 Jul 22. PMID:12138093 doi:http://dx.doi.org/10.1074/jbc.M202310200
- ↑ Truscott KN, Wiedemann N, Rehling P, Muller H, Meisinger C, Pfanner N, Guiard B. Mitochondrial import of the ADP/ATP carrier: the essential TIM complex of the intermembrane space is required for precursor release from the TOM complex. Mol Cell Biol. 2002 Nov;22(22):7780-9. PMID:12391147
- ↑ Wiedemann N, Truscott KN, Pfannschmidt S, Guiard B, Meisinger C, Pfanner N. Biogenesis of the protein import channel Tom40 of the mitochondrial outer membrane: intermembrane space components are involved in an early stage of the assembly pathway. J Biol Chem. 2004 Apr 30;279(18):18188-94. Epub 2004 Feb 20. PMID:14978039 doi:http://dx.doi.org/10.1074/jbc.M400050200
- ↑ Vergnolle MA, Baud C, Golovanov AP, Alcock F, Luciano P, Lian LY, Tokatlidis K. Distinct domains of small Tims involved in subunit interaction and substrate recognition. J Mol Biol. 2005 Aug 26;351(4):839-49. PMID:16039669 doi:http://dx.doi.org/S0022-2836(05)00660-1
- ↑ Koehler CM, Merchant S, Oppliger W, Schmid K, Jarosch E, Dolfini L, Junne T, Schatz G, Tokatlidis K. Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins. EMBO J. 1998 Nov 16;17(22):6477-86. PMID:9822593 doi:http://dx.doi.org/10.1093/emboj/17.22.6477
- ↑ Adam A, Endres M, Sirrenberg C, Lottspeich F, Neupert W, Brunner M. Tim9, a new component of the TIM22.54 translocase in mitochondria. EMBO J. 1999 Jan 15;18(2):313-9. PMID:9889188 doi:http://dx.doi.org/10.1093/emboj/18.2.313
- ↑ Baker MJ, Webb CT, Stroud DA, Palmer CS, Frazier AE, Guiard B, Chacinska A, Gulbis JM, Ryan MT. Structural and Functional Requirements for Activity of the Tim9-Tim10 Complex in Mitochondrial Protein Import. Mol Biol Cell. 2008 Nov 26. PMID:19037098 doi:E08-09-0903
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