2CW9

Crystal structure of human Tim44 C-terminal domain

Summary for 2CW9

• Entry DOI: 10.2210/pdb2cw9/pdb
• Descriptor: translocase of inner mitochondrial membrane, PENTAETHYLENE GLYCOL (3 entities in total)
• Functional Keywords: structure genomics, tim, structural genomics, nppfsa, riken structural genomics/proteomics initiative, rsgi, nppsfa, national project on protein structural and functional analyses, protein transport
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion inner membrane: O43615
• Total number of polymer chains: 1
• Total formula weight: 22411.58

Authors

Handa, N.,Kishishita, S.,Morita, S.,Kinoshita, Y.,Nagano, Y.,Uda, H.,Terada, T.,Uchikubo, T.,Takemoto, C.,Jin, Z.,Chrzas, J.,Chen, L.,Liu, Z.-J.,Wang, B.-C.,Shirouzu, M.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2005-06-17, release date: 2005-12-17, Last modification date: 2011-07-13)

Primary citation

Handa, N.,Kishishita, S.,Morita, S.,Akasaka, R.,Jin, Z.,Chrzas, J.,Chen, L.,Liu, Z.J.,Wang, B.C.,Sugano, S.,Tanaka, A.,Terada, T.,Shirouzu, M.,Yokoyama, S.
Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form.
Acta Crystallogr.,Sect.D, 63:1225-1234, 2007

PubMed 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.

PubMed: 18084070
DOI: 10.1107/S0907444907051463

Experimental method

X-RAY DIFFRACTION (1.9 Å)