Mapping protein interactions in the active TOM-TIM23 supercomplex

2021-09-29 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Mapping protein interactions in the active TOM-TIM23 supercomplex​
Gomkale, R.; Linden, A.; Neumann, P.; Schendzielorz, A. B.; Stoldt, S.; Dybkov, O. & Kilisch, M. et al.​ (2021) 
Nature Communications12(1) art. 5715​.​ DOI: 

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Gomkale, Ridhima; Linden, Andreas; Neumann, Piotr; Schendzielorz, Alexander Benjamin; Stoldt, Stefan; Dybkov, Olexandr; Kilisch, Markus; Schulz, Christian; Cruz-Zaragoza, Luis Daniel; Schwappach, Blanche; Ficner, Ralf; Jakobs, Stefan; Urlaub, Henning; Rehling, Peter
Abstract Nuclear-encoded mitochondrial proteins destined for the matrix have to be transported across two membranes. The TOM and TIM23 complexes facilitate the transport of precursor proteins with N-terminal targeting signals into the matrix. During transport, precursors are recognized by the TIM23 complex in the inner membrane for handover from the TOM complex. However, we have little knowledge on the organization of the TOM-TIM23 transition zone and on how precursor transfer between the translocases occurs. Here, we have designed a precursor protein that is stalled during matrix transport in a TOM-TIM23-spanning manner and enables purification of the translocation intermediate. Combining chemical cross-linking with mass spectrometric analyses and structural modeling allows us to map the molecular environment of the intermembrane space interface of TOM and TIM23 as well as the import motor interactions with amino acid resolution. Our analyses provide a framework for understanding presequence handover and translocation during matrix protein transport.
The TOM and TIM23 complexes facilitate the transport of nuclear-encoded proteins into the mitochondrial matrix. Here, the authors use a stalled client protein to purify the translocation supercomplex and gain insight into the TOM-TIM23 interface and the mechanism of protein handover from the TOM to the TIM23 complex.
Issue Date
Nature Communications 
EXC 2067: Multiscale Bioimaging 
SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente 
SFB 1190 | P01: Untersuchung der Unterschiede in der Zusammensetzung, Funktion und Position von individuellen MICOS Komplexen in einzelnen Säugerzellen 
SFB 1190 | P04: Der GET-Rezeptor als ein Eingangstor zum ER und sein Zusammenspiel mit GET bodies 
SFB 1190 | P13: Protein Transport über den mitochondrialen Carrier Transportweg 
SFB 1190 | Z02: Massenspektrometrie-basierte Proteomanalyse 
Working Group
RG Ficner (Molecular Structural Biology) 
RG Jakobs (Structure and Dynamics of Mitochondria) 
RG Rehling (Mitochondrial Protein Biogenesis) 
RG Schwappach (Membrane Protein Biogenesis) 
RG Urlaub (Bioanalytische Massenspektrometrie) 
External URL
Deutsche Forschungsgemeinschaft (German Research Foundation)



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