Article
- The EMBO Journal (2006) 25, 4675 - 4685
- doi:10.1038/sj.emboj.7601334
Published online: 14 September 2006
Subject Categories:
Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor
Dejana Mokranjac1, Gleb Bourenkov2, Kai Hell1, Walter Neupert1 and Michael Groll1
- Institute for Physiological Chemistry, Ludwig-Maximilians University, Munich, Germany
- Max-Planck-Group for Structural Molecular Biology at DESY, Hamburg, Germany
Correspondence to:
Walter Neupert, Institute for Physiological Chemistry, Ludwig-Maximilians University, Butenandtstr. 5, 81377 Munich, Germany. Tel.: +49 89 2180 77094; Fax +49 89 2180 77093; E-mail: neupert@med.uni-muenchen.de
Received 29 May 2006; Accepted 16 August 2006
Abstract
The import motor of the mitochondrial translocase of the inner membrane (TIM23) mediates the ATP-dependent translocation of preproteins into the mitochondrial matrix by cycles of binding to and release from mtHsp70. An essential step of this process is the stimulation of the ATPase activity of mtHsp70 performed by the J cochaperone Tim14. Tim14 forms a complex with the J-like protein Tim16. The crystal structure of this complex shows that the conserved domains of the two proteins have virtually identical folds but completely different surfaces enabling them to perform different functions. The Tim14–Tim16 dimer reveals a previously undescribed arrangement of J and J-like domains. Mutations that destroy the complex between Tim14 and Tim16 are lethal demonstrating that complex formation is an essential requirement for the viability of cells. We further demonstrate tight regulation of the cochaperone activity of Tim14 by Tim16. The first crystal structure of a J domain in complex with a regulatory protein provides new insights into the function of the mitochondrial TIM23 translocase and the Hsp70 chaperone system in general.
Keywords:
- chaperone,
- mitochondria,
- protein translocation
