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3.A.8.1.1
Mitochondrial protein translocase (MPT) (Chacinska et al., 2005; Mokranjac et al., 2005; Bihlmaier et al., 2007). The crystal structure of the intermembrane space domain of yeast Tim50 has been solved to 1.83 Å resolution (Qian et al., 2011). A protruding beta-hairpin of Tim50 is crucial for interaction with Tim23, providing a molecular basis for the cooperation of Tim50 and Tim23 in preprotein translocation to the protein-conducting channel of the mitochondrial inner membrane (Qian et al., 2011).  TIM23-mediates insertion of transmembrane α-helices into the mitochondrial inner membrane (Botelho et al., 2011). The TIM23 channel undergoes structural changes in response to the energized state of the membrane, the pmf (Malhotra et al. 2013).  TMS1 in TIM23 is required for homodimerization while it and TMS2 are involved in pre-protein binding in the channel (Pareek et al. 2013).  The Tom40 outer membrane channel may be a 19 β-stranded barrel, possibly homologous to the VDAC porins (TC# 1.B.8) (Lackey et al. 2014).  Tim23 and Tim17 interact with each other as well as Tim44 and Pam17, respectively.  These last two proteins may serve regulatory functions (Ting et al. 2014).  Tom20, 22, 40 and 70 recognize presequences in various mitochondrially targetted proteins (Melin et al. 2015; Melin et al. 2014).  In the 4 TMS TIM17 protein, mutations in TMSs1 and 2 impair the interaction of Tim17 with Tim23, whereas mutations in TM3 compromise binding of the import motor (Demishtein-Zohary et al. 2017); further, residues in the matrix-facing region of Tim17 involved in binding of the import motor were identified. TIM22, forms an intramolecular disulfide bond in yeast and humans.  If not oxidized, they do not properly integrate into the membrane complex, and the lack of Tim17 oxidation disrupts the TIM23 translocase complex (Wrobel et al. 2016). Mgr2 (TC# 1.A.111.1.3) and Pam18 are involved in precursormembrane protein quality control (Schendzielorz et al. 2018). Tom7 and OMA1 play reciprocal roles during mitochondrial import and activation of the PTEN-induced kinase 1, PINK1, in humans (Sekine et al. 2019).  Organellar beta-barrel proteins are unique as most of them do not contain typical targeting information in the form of an N-terminal cleavable targeting signal. Instead, targeting and surface recognition of mitochondrial beta-barrel proteins in yeast, humans and plants depends on the hydrophobicity of the last beta-hairpin of the beta-barrel. Klinger et al. 2019 demonstrated that hydrophobicity is not sufficient for the discrimination of targeting to chloroplasts or mitochondria. Using atVDAC1 (TC# 1.B.8.1.15) and psOEP24 (1.B.28.1.1) they showed that the presence of a hydrophilic amino acid at the C-terminus of the penultimate beta-strand is required for mitochondrial targeting. A mutation of the chloroplast beta-barrel protein psOEP24 which mimics such a profile is efficiently targeted to mitochondria (Klinger et al. 2019). The high-resolution cryo-EM structures of the core TOM complex from Saccharomyces cerevisiae in dimeric and tetrameric forms have  been determined (Tucker and Park 2019). Dimeric TOM consists of two copies each of five proteins arranged in two-fold symmetry: pore-forming beta-barrel protein Tom40 and four auxiliary alpha-helical transmembrane proteins. The pore of each Tom40 has an overall negatively charged inner surface due to multiple functionally important acidic patches. The tetrameric complex is a dimer of dimeric TOM, which may be capable of forming higher-order oligomers. Negatively charged residues in the N-terminus of Tim17 are critical for the preprotein-induced gating of the TIM23 translocase, possibly by recognizing the positive charges in the leader sequence of the substrate proteins (Meier et al. 2005).  

Accession Number:O74700
Protein Name:Tim9 YEL020W-A aka YEL020BW
Length:87
Molecular Weight:10202.00
Species:Saccharomyces cerevisiae (Baker's yeast) [4932]
Location1 / Topology2 / Orientation3: Mitochondrion inner membrane1 / Peripheral membrane protein2 / Intermembrane side3
Substrate proteins

Cross database links:

Genevestigator: O74700
eggNOG: fuNOG10876
HEGENOM: HBG628226
DIP: DIP-5806N
RefSeq: NP_010894.1   
Entrez Gene ID: 856693   
Pfam: PF02953   
KEGG: sce:YEL020W-A   

Gene Ontology

GO:0042721 C:mitochondrial inner membrane protein insert...
GO:0042719 C:mitochondrial intermembrane space protein t...
GO:0046872 F:metal ion binding
GO:0008565 F:protein transporter activity
GO:0051082 F:unfolded protein binding
GO:0045039 P:protein import into mitochondrial inner mem...
GO:0055085 P:transmembrane transport

References (15)

[1] “Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins.”  Koehler C.M.et.al.   9822593
[2] “The nucleotide sequence of Saccharomyces cerevisiae chromosome V.”  Dietrich F.S.et.al.   9169868
[3] “Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae.”  Hu Y.et.al.   17322287
[4] “Tim9, a new component of the TIM22.54 translocase in mitochondria.”  Adam A.et.al.   9889188
[5] “The structural basis of the TIM10 chaperone assembly.”  Lu H.et.al.   14973126
[6] “Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex.”  Endres M.et.al.   10369662
[7] “Two intermembrane space TIM complexes interact with different domains of Tim23p during its import into mitochondria.”  Davis A.J.et.al.   10995434
[8] “Functional reconstitution of the import of the yeast ADP/ATP carrier mediated by the TIM10 complex.”  Luciano P.et.al.   11483513
[9] “The essential function of the small Tim proteins in the TIM22 import pathway does not depend on formation of the soluble 70-kilodalton complex.”  Murphy M.P.et.al.   11509656
[10] “The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier.”  Curran S.P.et.al.   11867522
[11] “Assembly of Tim9 and Tim10 into a functional chaperone.”  Vial S.et.al.   12138093
[12] “Mitochondrial import of the ADP/ATP carrier: the essential TIM complex of the intermembrane space is required for precursor release from the TOM complex.”  Truscott K.N.et.al.   12391147
[13] “The role of Tim9p in the assembly of the TIM22 import complexes.”  Leuenberger D.et.al.   12656987
[14] “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.”  Wiedemann N.et.al.   14978039
[15] “Distinct domains of small Tims involved in subunit interaction and substrate recognition.”  Vergnolle M.A.S.et.al.   16039669
Structure:
3DXR     

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FASTA formatted sequence
1:	MDALNSKEQQ EFQKVVEQKQ MKDFMRLYSN LVERCFTDCV NDFTTSKLTN KEQTCIMKCS 
61:	EKFLKHSERV GQRFQEQNAA LGQGLGR