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Defining the architecture of the human TIM22 complex by chemical crosslinking
Author(s) -
Valpadashi Anusha,
Callegari Sylvie,
Linden Andreas,
Neumann Piotr,
Ficner Ralf,
Urlaub Henning,
Deckers Markus,
Rehling Peter
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13978
Subject(s) - translocase , molecular machine , chaperone (clinical) , translocase of the inner membrane , mitochondrion , transmembrane protein , inner membrane , biophysics , chromosomal translocation , inner mitochondrial membrane , chemistry , translocase of the outer membrane , nuclear pore , mitochondrial carrier , microbiology and biotechnology , biochemistry , biology , mitochondrial membrane transport protein , bacterial outer membrane , cytoplasm , genetics , escherichia coli , medicine , receptor , pathology , gene
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.