title: Tim22, the essential core of the mitochondrial protein insertion complex, forms a voltage-activated and signal-gated channel.
abstract: The protein insertion complex of the mitochondrial inner membrane is crucial for import of the numerous multitopic membrane proteins with internal targeting signals. Little is known about the molecular mechanism of this complex, including whether it forms a real channel or merely acts as scaffold for protein insertion. We report the unexpected observation that Tim22 is the only essential membrane-integrated subunit of the complex. Reconstituted Tim22 forms a hydrophilic, high-conductance channel with distinct opening states and pore diameters. The channel is voltage-activated and specifically responds to an internal targeting signal, but not to presequences. Thus, a protein insertion complex can combine three essential functions, signal recognition, channel formation, and energy transduction, in one central component.
authors.affiliation: Biophysik, Universität Osnabrück, FB Biologie/Chemie, D-49034 Osnabrück, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovermann
authors.forename: Kaye N
authors.initials: KN
authors.lastname: Truscott
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.forename: Naresh B
authors.initials: NB
authors.lastname: Sepuri
authors.forename: Hanne
authors.initials: H
authors.lastname: Müller
authors.forename: Robert E
authors.initials: RE
authors.lastname: Jensen
authors.forename: Richard
authors.initials: R
authors.lastname: Wagner
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism; D017353:Gene Deletion; D006238:Haploidy; D007425:Intracellular Membranes / Q000737:chemistry / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008081:Liposomes; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D021382:Protein Sorting Signals / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D008081:Liposomes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C102549:TIM22 protein, S cerevisiae; C110036:TIM54 protein, S cerevisiae