Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form
- U of Tokyo
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 {angstrom} 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 {alpha} 1 and {alpha} 2 helices near Pro308. A comparison with the yeast homolog revealed that lipid binding induces conformational changes around the {alpha} 1-{alpha} 2 loop, leading to slippage of the {alpha} 1 helix along the large {beta}-sheet. These changes may play important roles in the translocation of polypeptides across the mitochondrial inner membrane.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1007628
- Journal Information:
- Acta Crystallogr. D, Vol. 63, Issue (12) ; 12, 2007; ISSN 0907-4449
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
The POTRA domains of Toc75 exhibit chaperone-like function to facilitate import into chloroplasts
Crystal Structure of Bovine Mitochondrial Factor B at 0.96-Angstrom Resolution