Insights into conformational changes occurring during the early steps of cytochrome b maturation

Carlström, Andreas,1988-Stockholms universitet,Institutionen för biokemi och biofysik,Martin Ott (author)

Membrane proteins carrying redox cofactors are key subunits of respiratory chain complexes, yet the exact path of their folding and maturation remains poorly understood. Here, using cryo-EM and structure prediction via Alphafold2, we generated models of the early assembly intermediates of cytochrome b (Cytb), a central catalytic subunit of complex III, indicating which conformational changes could occur during its assembly. Previous work has shown that newly synthesized Cytb progresses through a series of assembly intermediates that support heme co-factor acquisition, steps that need to occur before the protein is joined with further subunits of the fully mature complex III. The predicted structure of the first assembly intermediate suggests how binding of Cytb to the assembly factor Cbp3-Cbp6 imposes an open configuration, which should facilitate acquisition of its heme cofactors. Moreover, structure predictions of the second intermediate indicate how these hemes get stabilized by binding of the subsequent assembly factor Cbp4, with a concomitant weakening of the contact between Cbp3-Cbp6 and Cytb, preparing a release of the fully hemylated protein from the assembly factors. These results therefore allow to formulate a hypothesis about the structural rearrangements as they occur during biogenesis of Cytb.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
Mitochondria
Respiratory chain
Membrane protein assembly
Biogenesis
Cytochrome b
biokemi
Biochemistry

Ott, MartinStockholms universitet,Institutionen för biokemi och biofysik,Göteborgs universitet (author)
Stockholms universitetInstitutionen för biokemi och biofysik (creator_code:org_t)

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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