Cryo-EM shows multiple cytochrome P450 reductase conformations

What the study found: Rat cytochrome P450 reductase (CPR), a diflavin-containing enzyme involved in electron transfer, was found by cryo-electron microscopy (cryo-EM) to adopt a compact conformation in solution. The structure also showed additional, less common compact variants and a subset of molecules with the FMN-binding domain either not visible or positioned far from the rest of the catalytic core.
Why the authors say this matters: The authors conclude that these observations support large-scale interdomain rearrangements as the structural basis for CPR function. They also suggest that cryo-EM can help uncover the molecular mechanisms of the CPR-mediated electron transfer cycle.
What the researchers tested: The researchers determined a 3.3 Å cryo-EM structure of full-length rat CPR, which they describe as the first electron microscopy structure of this 77 kDa protein. They compared the solution structure with previously available crystal structures.
What worked and what didn't: The full-length, fully active enzyme was observed in a compact state, but this state was described as more relaxed than in crystal structures. Less populated compact conformations were also identified, and about 20% of molecules showed the FMN-binding domain not visible or displaced far from the catalytic core.
What to keep in mind: The abstract does not describe experimental limitations beyond noting that some conformations were less populated. The summary is limited to the findings stated in the abstract.

Key points

• Cryo-EM revealed a compact solution structure of full-length rat cytochrome P450 reductase.
• The structure was reported at 3.3 Å resolution and described as the first electron microscopy structure of this 77 kDa protein.
• Less common compact conformations were also observed, along with a subset of molecules in which the FMN-binding domain was not visible or was far from the catalytic core.
• The authors say the findings support large-scale interdomain rearrangements as the basis of CPR function.
• The authors suggest cryo-EM may help explain the CPR-mediated electron transfer cycle.