Defining the architecture of the human TIM22 complex by chemical crosslinking

FEBS Letters

article

Anusha Valpadashi¹  Sylvie Callegari¹  Andreas Linden⁴  Piotr Neumann⁶  Ralf Ficner⁶  Henning Urlaub⁴  Markus Deckers¹  Peter Rehling¹ 

[1] Department of Cellular Biochemistry, University Medical Center Göttingen;Ubiquitin Signalling Division, The Walter and Eliza Hall Institute of Medical Research;Department of Medical Biology, University of Melbourne;Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry;Department of Clinical Chemistry, Bioanalytics, University Medical Center Göttingen;Department of Molecular Structural Biology, Institute for Microbiology and Genetics, Göttingen Center for Molecular Biosciences, Georg-August-University Göttingen;Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” ,(MBExC), University of Goettingen;Max Planck Institute for Biophysical Chemistry

关键词: carrier translocase;    crosslinking-mass spectrometry;    mitochondria;    protein translocation;    TIM22;   

DOI  :  10.1002/1873-3468.13978

来源: John Wiley & Sons Ltd.

【 摘 要 】

The majority of mitochondrial proteins are nuclear encoded and imported into mitochondria as precursor proteins via dedicated translocases. The translocase of the inner membrane 22 (TIM22) is a multisubunit molecular machine specialized for the translocation of hydrophobic, multi-transmembrane-spanning proteins with internal targeting signals into the inner mitochondrial membrane. Here, we undertook a crosslinking-mass spectrometry (XL-MS) approach to determine the molecular arrangement of subunits of the human TIM22 complex. Crosslinking of the isolated TIM22 complex using the BS3 crosslinker resulted in the broad generation of crosslinks across the majority of TIM22 components, including the small TIM chaperone complex. The crosslinking data uncovered several unexpected features, opening new avenues for a deeper investigation into the steps required for TIM22-mediated translocation in humans.

【 授权许可】

Unknown