InterPro domain: IPR004217

This domain has four conserved cysteine residues. It is found in proteins Tim8, Tim9, Tim10 and Tim13, which are involved in mitochondrial protein import [ 1 ] and seem to be localised to the mitochondrial intermembrane space. The Tim8-Tim13 complex has a complex architecture, similar to the Tim9-Tim10 complex, composed of a hexametric architecture with long helices which look like tentacles extend from a central loop [ 2 ]. In each subunit of the Tim9-Tim10 complex, a signature "twin CX3C" motif forms two intramolecular disulfides [ 3 ].

Defects in the Tim8A gene (DDP1) have been shown to be the cause of 2 human syndromes: Mohr-Tranebjaerg syndrome (MTS); also known as dystonia-deafness syndrome (DDS) or X-linked progressive deafness type 1 (DFN-1); and Jensen syndrome (JENSS); also known as opticoacoustic nerve atrophy with dementia.

1. The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J. 19, 6392-400
2. The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23. J. Mol. Biol. 382, 1144-56
3. Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller. Mol. Cell 21, 123-33