PDBsum entry 2cw9

Protein transport

PDB id: 2cw9

Contents

Protein chain

182 a.a. *

Ligands

1PE ×2

Waters ×151

* Residue conservation analysis

PDB id:

2cw9

Name:

Protein transport

Title:

Crystal structure of human tim44 c-terminal domain

Structure:

Translocase of inner mitochondrial membrane. Chain: a. Fragment: c-terminal domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: cell free

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.218 R-free: 0.221

Authors:

N.Handa,S.Kishishita,S.Morita,Y.Kinoshita,Y.Nagano,H.Uda,T.Terada, T.Uchikubo,C.Takemoto,Z.Jin,J.Chrzas,L.Chen,Z.-J.Liu,B.-C.Wang, M.Shirouzu,S.Yokoyama,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

N.Handa et al. (2007). Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form. Acta Crystallogr D Biol Crystallogr, 63, 1225-1234. PubMed id: 18084070 DOI: 10.1107/S0907444907051463

Date:

17-Jun-05 Release date: 17-Dec-05

Protein chain

O43615  (TIM44_HUMAN) -  Mitochondrial import inner membrane translocase subunit TIM44 from Homo sapiens

Seq: 452 a.a.

Struc: 182 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1107/S0907444907051463

Acta Crystallogr D Biol Crystallogr 63:1225-1234 (2007)

PubMed id: 18084070

Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form.

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.

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.

Selected figure(s)

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 ).

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.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 1225-1234) copyright 2007.

Figures were selected by an automated process.