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PDBsum entry 2cw9
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Protein transport
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PDB id
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2cw9
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References listed in PDB file
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Key reference
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Title
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Structure of the human tim44 c-Terminal domain in complex with pentaethylene glycol: ligand-Bound form.
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Authors
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N.Handa,
S.Kishishita,
S.Morita,
R.Akasaka,
Z.Jin,
J.Chrzas,
L.Chen,
Z.J.Liu,
B.C.Wang,
S.Sugano,
A.Tanaka,
T.Terada,
M.Shirouzu,
S.Yokoyama.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2007,
63,
1225-1234.
[DOI no: ]
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PubMed id
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Abstract
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Familial oncocytic thyroid carcinoma is associated with a missense mutation,
P308Q, in the C-terminal domain of Tim44. Tim44 is the mitochondrial
inner-membrane translocase subunit and it functions as a membrane anchor for the
mitochondrial heat-shock protein 70 (mtHsp70). Here, the crystal structure of
the human Tim44 C-terminal domain complexed with pentaethylene glycol has been
determined at 1.9 A resolution. The overall structure resembles that of the
nuclear transport factor 2-like domain. In the crystal structure, pentaethylene
glycol molecules are associated at two potential membrane-binding sites: the
large hydrophobic cavity and the highly conserved loop between the alpha1 and
alpha2 helices near Pro308. A comparison with the yeast homolog revealed that
lipid binding induces conformational changes around the alpha1-alpha2 loop,
leading to slippage of the alpha1 helix along the large beta-sheet. These
changes may play important roles in the translocation of polypeptides across the
mitochondrial inner membrane.
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Figure 3.
Figure 3 Surface representation and ribbon diagram of the human
Tim44 C-terminal domain. (a) Blue and red surfaces represent
positive and negative potentials, respectively. The figure is in
the same orientation as that in Fig. 1-(a). Two pentaethylene
glycol binding sites are indicated by arrows. This figure was
drawn using APBS (http://apbs.sourceforge.net/ ) and PyMOL
(http://www.pymol.org ). (b) The residues are colored according
to sequence conservation, ranging from white (variable residues)
to orange (conserved residues). This figure was drawn using
ClustalX (Thompson et al., 1997[Thompson, J. D., Gibson, T. J.,
Plewniak, F., Jeanmougin, F. & Higgins, D. G. (1997). Nucleic
Acids Res. 25, 4876-4882.]), CONSURF (Glaser et al.,
2003[Glaser, F., Pupko, T., Paz, I., Bell, R. E.,
Bechor-Shental, D., Martz, E. & Ben-Tal, N. (2003).
Bioinformatics, 19, 163-164.]) and PyMOL (http://www.pymol.org ).
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Figure 7.
Figure 7 Cartoon representation of the interaction of the  1
helix and the  -sheet
of human Tim44 (stereoview). The residues that interact by
direct or water-mediated hydrogen bonds are shown as stick
models. The interacting water molecules are shown as red dots.
Hydrogen bonds are indicated by red dashed lines.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2007,
63,
1225-1234)
copyright 2007.
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