2cw9

Publication Abstract from PubMed

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.

Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form.,Handa N, Kishishita S, Morita S, Akasaka R, Jin Z, Chrzas J, Chen L, Liu ZJ, Wang BC, Sugano S, Tanaka A, Terada T, Shirouzu M, Yokoyama S Acta Crystallogr D Biol Crystallogr. 2007 Dec;63(Pt 12):1225-34. Epub 2007, Nov 16. PMID:18084070^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.