Tim22, the essential core of the mitochondrial protein insertion complex, forms a voltage-activated and signal-gated channel.
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.
Kovermann
Peter
P
Biophysik, Universität Osnabrück, FB Biologie/Chemie, D-49034 Osnabrück, Germany.
Truscott
Kaye N
KN
Guiard
Bernard
B
Rehling
Peter
P
Sepuri
Naresh B
NB
Müller
Hanne
H
Jensen
Robert E
RE
Wagner
Richard
R
Pfanner
Nikolaus
N
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
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