Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form - PubMed (original) (raw)
. 2007 Dec;63(Pt 12):1225-34.
doi: 10.1107/S0907444907051463. Epub 2007 Nov 16.
Seiichiro Kishishita, Satoshi Morita, Ryogo Akasaka, Zhongmin Jin, John Chrzas, Lirong Chen, Zhi-Jie Liu, Bi-Cheng Wang, Sumio Sugano, Akiko Tanaka, Takaho Terada, Mikako Shirouzu, Shigeyuki Yokoyama
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- PMID: 18084070
- DOI: 10.1107/S0907444907051463
Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form
Noriko Handa et al. Acta Crystallogr D Biol Crystallogr. 2007 Dec.
Abstract
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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