The essential function of Tim12 in vivo is ensured by the assembly interactions of its C-terminal domain

Eirini Lionaki; Carine de Marcos Lousa; Catherine Baud; Maria Vougioukalaki; George Panayotou; Kostas Tokatlidis

doi:10.1074/jbc.M800350200

The essential function of Tim12 in vivo is ensured by the assembly interactions of its C-terminal domain

J Biol Chem. 2008 Jun 6;283(23):15747-53. doi: 10.1074/jbc.M800350200. Epub 2008 Apr 3.

Authors

Eirini Lionaki¹, Carine de Marcos Lousa, Catherine Baud, Maria Vougioukalaki, George Panayotou, Kostas Tokatlidis

Affiliation

¹ Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion 71110, Crete, Greece.

Abstract

The small Tims chaperone hydrophobic precursors across the mitochondrial intermembrane space. Tim9 and Tim10 form the soluble TIM10 complex that binds precursors exiting from the outer membrane. Tim12 functions downstream, as the only small Tim peripherally attached on the inner membrane. We show that Tim12 has an intrinsic affinity for inner mitochondrial membrane lipids, in contrast to the other small Tims. We find that the C-terminal end of Tim12 is essential in vivo. Its deletion crucially abolishes assembly of Tim12 in complexes with the other Tims. The N-terminal end contains targeting information and also mediates direct binding of Tim12 to the transmembrane segments of the carrier substrates. These results provide a molecular basis for the concept that the essential role of Tim12 relies on its unique assembly properties that allow this subunit to bridge the soluble and membrane-embedded translocases in the carrier import pathway.

Publication types

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

MeSH terms

Amino Acid Sequence
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Membrane Transport Proteins / genetics
Membrane Transport Proteins / metabolism
Mitochondrial Membrane Transport Proteins
Mitochondrial Membranes / metabolism*
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Multiprotein Complexes / genetics
Multiprotein Complexes / metabolism
Protein Structure, Tertiary / physiology
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Sequence Deletion

Substances

Membrane Proteins
Membrane Transport Proteins
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins
Multiprotein Complexes
Saccharomyces cerevisiae Proteins
TIM10 protein, S cerevisiae
TIM12 protein, S cerevisiae
Tim9 protein, S cerevisiae