Solution structure of the cytochrome P450 reductase-cytochrome c complex determined by neutron scattering

The Journal of Biological Chemistry
Samuel L FreemanGordon C K Roberts

Abstract

Electron transfer in all living organisms critically relies on formation of complexes between the proteins involved. The function of these complexes requires specificity of the interaction to allow for selective electron transfer but also a fast turnover of the complex, and they are therefore often transient in nature, making them challenging to study. Here, using small-angle neutron scattering with contrast matching with deuterated protein, we report the solution structure of the electron transfer complex between cytochrome P450 reductase (CPR) and its electron transfer partner cytochrome c This is the first reported solution structure of a complex between CPR and an electron transfer partner. The structure shows that the interprotein interface includes residues from both the FMN- and FAD-binding domains of CPR. In addition, the FMN is close to the heme of cytochrome c but distant from the FAD, indicating that domain movement is required between the electron transfer steps in the catalytic cycle of CPR. In summary, our results reveal key details of the CPR catalytic mechanism, including interactions of two domains of the reductase with cytochrome c and motions of these domains relative to one another. These findings shed light...Continue Reading

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Citations

Dec 29, 2019·Scientific Reports·Ana C EbrechtDiederik J Opperman
Jan 28, 2021·International Journal of Molecular Sciences·Manuel SellnerMartin Smieško
Jan 18, 2019·Journal of Structural Biology·Angela M TavolieriM Elizabeth Stroupe
Mar 17, 2021·Journal of Structural Biology·Daniel T MurrayM Elizabeth Stroupe
May 14, 2021·Chemical Communications : Chem Comm·Bankala KrishnarjunaAyyalusamy Ramamoorthy
Oct 5, 2021·Acta Crystallographica. Section D, Structural Biology·Gabriela C Schröder, Flora Meilleur

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Methods Mentioned

BETA
NMR
X-ray
small-angle neutron scattering
SANS
neutron scattering
size
small-angle
size exclusion chromatography

Software Mentioned

SUPALM
ATSAS
SASpy
GRASP
HADDOCK
GNOM
DAMAVER
PyMOL
DAMFILT
MultiFoXS

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