Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor

Dejana Mokranjac; Gleb Bourenkov; Kai Hell; Walter Neupert; Michael Groll

doi:10.1038/sj.emboj.7601334

Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor

EMBO J. 2006 Oct 4;25(19):4675-85. doi: 10.1038/sj.emboj.7601334. Epub 2006 Sep 14.

Authors

Dejana Mokranjac¹, Gleb Bourenkov, Kai Hell, Walter Neupert, Michael Groll

Affiliation

¹ Institute for Physiological Chemistry, Ludwig-Maximilians University, Munich, Germany.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Crystallography, X-Ray
Dimerization
Evolution, Molecular
Membrane Transport Proteins / chemistry*
Membrane Transport Proteins / metabolism*
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins / chemistry*
Mitochondrial Proteins / metabolism*
Models, Molecular
Molecular Motor Proteins / chemistry
Molecular Motor Proteins / metabolism
Molecular Sequence Data
Protein Structure, Secondary
Protein Structure, Tertiary
Protein Subunits / chemistry
Protein Subunits / metabolism
Protein Transport
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / metabolism*
Sequence Alignment
Structure-Activity Relationship

Substances

Membrane Transport Proteins
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins
Molecular Motor Proteins
Pam16 protein, S cerevisiae
Protein Subunits
Saccharomyces cerevisiae Proteins
Tim14 protein, S cerevisiae