Structural basis for the interaction of the chaperone Cbp3 with newly synthesized cytochrome b during mitochondrial respiratory chain assembly

DOI: 10.1074/jbc.RA119.010483

Authors: Mama Ndi (Stockholm University) , Geoffrey Masuyer (Stockholm University) , Hannah Dawitz (Stockholm University) , Andreas Carlström (Stockholm University) , Mirco Michel (Stockholm University) , Arne Elofsson (Stockholm University) , Mikaela Rapp (Stockholm University) , Pal Stenmark (Stockholm University) , Martin Ott (Stockholm University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry

State: Published (Approved)
Published: September 2019
Diamond Proposal Number(s): 11265

Abstract: Assembly of the mitochondrial respiratory chain requires the coordinated synthesis of mitochondrial and nuclear encoded subunits, redox co-factor acquisition, and correct joining of the subunits to form functional complexes. The conserved Cbp3–Cbp6 chaperone complex binds newly synthesized cytochrome b and supports the ordered acquisition of the heme co-factors. Moreover, it functions as a translational activator by interacting with the mitoribosome. Cbp3 consists of two distinct domains, an N-terminal domain present in mitochondrial Cbp3 homologs, and a highly conserved C-terminal domain comprising a ubiquinol–cytochrome c chaperone region. Here, we solved the crystal structure of this C-terminal domain from a bacterial homolog at 1.4 Å resolution, revealing a unique all-helical fold. This structure allowed mapping of the interaction sites of yeast Cbp3 with Cbp6 and cytochrome b via site-specific photo-crosslinking. We propose that mitochondrial Cbp3 homologs carry an N-terminal extension that positions the conserved C-terminal domain at the ribosomal tunnel exit for an efficient interaction with its substrate, the newly synthesized cytochrome b protein.

Journal Keywords: complex III; assembly factor; mMitochondrial translation; ubiquinol-cytochrome c chaperone domain; electron transfer chain; structural biology; protein assembly; mitochondria; membrane biogenesis; protein cross-linking; respiratory chain

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

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