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).
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) ]. This entry represents the C-terminal region of Tim44 that has been shown to form a stable proteolytic fragment in yeast. This region is also found in a set of smaller bacterial proteins. The molecular function of the bacterial members is unknown, but transport seems likely. The crystal structure of the C terminus of Tim44 has revealed a large hydrophobic pocket which might play an important role in interacting with the acyl chains of lipid molecules in the mitochondrial membrane [ (PUBMED:16647716) ].
Family alignment:
There are 9767 Tim44 domains in 9757 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing Tim44 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with Tim44 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing Tim44 domain in the selected taxonomic class.
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.
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.
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.
