title: Tim50's presequence receptor domain is essential for signal driven transport across the TIM23 complex.
abstract: N-terminal targeting signals (presequences) direct proteins across the TOM complex in the outer mitochondrial membrane and the TIM23 complex in the inner mitochondrial membrane. Presequences provide directionality to the transport process and regulate the transport machineries during translocation. However, surprisingly little is known about how presequence receptors interact with the signals and what role these interactions play during preprotein transport. Here, we identify signal-binding sites of presequence receptors through photo-affinity labeling. Using engineered presequence probes, photo cross-linking sites on mitochondrial proteins were mapped mass spectrometrically, thereby defining a presequence-binding domain of Tim50, a core subunit of the TIM23 complex that is essential for mitochondrial protein import. Our results establish Tim50 as the primary presequence receptor at the inner membrane and show that targeting signals and Tim50 regulate the Tim23 channel in an antagonistic manner.
authors: Abteilung für Biochemie II, Universität Göttingen, D-37073 Göttingen, Germany.
authors: Christian
authors: C
authors: Schulz
authors: Oleksandr
authors: O
authors: Lytovchenko
authors: Jonathan
authors: J
authors: Melin
authors: Agnieszka
authors: A
authors: Chacinska
authors: Bernard
authors: B
authors: Guiard
authors: Piotr
authors: P
authors: Neumann
authors: Ralf
authors: R
authors: Ficner
authors: Olaf
authors: O
authors: Jahn
authors: Bernhard
authors: B
authors: Schmidt
authors: Peter
authors: P
authors: Rehling
mesh_terms: D026901:Membrane Transport Proteins / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C083081:TIM23 protein, S cerevisiae; C469615:TIM50 protein, S cerevisiae