Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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Tim44

SMART accession number:	SM00978
Description:	Tim44 is an essential component of the machinery that mediates the translocation of nuclear-encoded proteins across the mitochondrial inner membrane (PUBMED:10430866). Tim44 is thought to bind phospholipids of the mitochondrial inner membrane both by electrostatic interactions and by penetrating the polar head group region (PUBMED:10430866).
Interpro abstract (IPR007379):	Tim44 is an essential component of the machinery that mediates the translocation of nuclear-encoded proteins across the mitochondrial inner membrane [(PUBMED:10430866)]. Tim44 is thought to bind phospholipids of the mitochondrial inner membrane both by electrostatic interactions and by penetrating the polar head group region [(PUBMED:10430866)].
GO process:	intracellular protein transport (GO:0006886)
GO component:	mitochondrial inner membrane presequence translocase complex (GO:0005744)
GO function:	P-P-bond-hydrolysis-driven protein transmembrane transporter activity (GO:0015450)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 816 Tim44 domains in 816 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a Tim44 domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with Tim44 domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Cellular role: transport
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Josyula R, Jin Z, McCombs D, DeLucas L, Sha B
  • Preliminary crystallographic studies of yeast mitochondrial peripheralmembrane protein Tim44p.
  • Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006; 62: 172-4
  • Display abstract

  • Protein translocations across mitochondrial membranes play critical rolesin mitochondrion biogenesis. Protein transport from the cell cytosol tothe mitochondrial matrix is carried out by the translocase of the outermembrane (TOM) complex and the translocase of the inner membrane (TIM)complexes. Tim44p is an essential mitochondrial peripheral membraneprotein and a major component of the TIM23 translocon. To investigate themechanism by which Tim44p functions in the TIM23 translocon to deliver themitochondrial protein precursors, the yeast Tim44p was crystallized. Thecrystals diffract to 3.2 A using a synchrotron X-ray source and belong tospace group P6(3)22, with unit-cell parameters a = 124.25, c = 77.83 A.There is one Tim44p molecule in one asymmetric unit, which corresponds toa solvent content of approximately 43%. Structure determination by MADmethods is under way.

  • Josyula R, Jin Z, Fu Z, Sha B
  • Crystal structure of yeast mitochondrial peripheral membrane proteinTim44p C-terminal domain.
  • J Mol Biol. 2006; 359: 798-804
  • Display abstract

  • The protein transports from the cell cytosol to the mitochondria matrixare carried out by the translocase of the outer membrane (TOM) complex andthe translocase of the inner membrane (TIM) complexes. Tim44p is anessential mitochondrial peripheral membrane protein and a major componentof TIM23 translocon. Tim44p can tightly associate with the innermitochondrial membrane. To investigate the mechanism by which Tim44pfunctions in the TIM23 translocon to deliver the mitochondrial proteinprecursors, we have determined the crystal structure of the yeast Tim44pC-terminal domain to 3.2A resolution using the MAD method. The Tim44pC-terminal domain forms a monomer in the crystal structure and containssix alpha-helices and four antiparallel beta-strands. A large hydrophobicpocket was identified on the Tim44p structure surface. The N-terminalhelix A1 is positively charged and the helix A1 protrudes out from theTim44p main body.

  • Weiss C et al.
  • Domain structure and lipid interaction of recombinant yeast Tim44.
  • Proc Natl Acad Sci U S A. 1999; 96: 8890-4
  • Display abstract

  • Tim44 is an essential component of the machinery that mediates thetranslocation of nuclear-encoded proteins across the mitochondrial innermembrane. It functions as a membrane anchor for the ATP-driven proteinimport motor whose other subunits are the mitochondrial 70-kDa heat-shockprotein (mhsp70) and its nucleotide exchange factor, mGrpE. To understandhow this motor is anchored to the inner membrane, we have overexpressedTim44 in Escherichia coli and studied the properties of the pure proteinand its interaction with model lipid membranes. Limited proteolysis andanalytical ultracentrifugation indicate that Tim44 is an elongated monomerwith a stably folded C-terminal domain. The protein binds strongly toliposomes composed of phosphatidylcholine and cardiolipin but only weaklyto liposomes containing phosphatidylcholine alone. Studies withphospholipid monolayers suggest that Tim44 binds to phospholipids of themitochondrial inner membrane both by electrostatic interactions and bypenetrating the polar head group region.

• Structure (3D structures containing this domain)

• 3D Structures of Tim44 domains in PDB

  PDB code	Main view	Title
  2cw9		Crystal structure of human tim44 c-terminal domain
  2fxt		Crystal structure of yeast tim44

• Links (links to other resources describing this domain)

• PFAM	Tim44
  INTERPRO	IPR007379

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