Molecular Basis of the Dynamic Structure of the TIM23 Complex in the Mitochondrial Intermembrane Space

• Tim23IMS contains multiple sites for binding to different partners
• Three Tim23IMS motifs bind to a single conserved pocket in Tim21IMS
• The C-terminal domain of Tim50IMS contributes to complex formation with Tim23IMS
• Tim23IMS dynamically regulates the presequence translocase

SummaryThe presequence translocase TIM23 is a highly dynamic complex in which its subunits can adopt multiple conformations and undergo association-dissociation to facilitate import of proteins into mitochondria. Despite the importance of protein-protein interactions in TIM23, little is known about the molecular details of these processes. Using nuclear magnetic resonance spectroscopy, we characterized the dynamic interaction network of the intermembrane space domains of Tim23, Tim21, Tim50, and Tom22 at single-residue level. We show that Tim23IMS contains multiple sites to efficiently interact with the intermembrane space domain of Tim21 and to bind to Tim21, Tim50, and Tom22. In addition, we reveal the atomic details of the dynamic Tim23IMS-Tim21IMS complex. The combined data support a central role of the intermembrane space domain of Tim23 in the formation and regulation of the presequence translocase.

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