Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Freeman, Samuel L., Martel, Anne, Devos, Juliette M., Basran, Jaswir, Raven, Emma L., Roberts, Gordon C. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892573/
https://www.ncbi.nlm.nih.gov/pubmed/29475945
http://dx.doi.org/10.1074/jbc.RA118.001941
_version_ 1783313188910006272
author Freeman, Samuel L.
Martel, Anne
Devos, Juliette M.
Basran, Jaswir
Raven, Emma L.
Roberts, Gordon C. K.
author_facet Freeman, Samuel L.
Martel, Anne
Devos, Juliette M.
Basran, Jaswir
Raven, Emma L.
Roberts, Gordon C. K.
author_sort Freeman, Samuel L.
collection PubMed
description 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 on interprotein electron transfer in this system and illustrate a powerful approach for studying solution structures of protein–protein complexes.
format Online
Article
Text
id pubmed-5892573
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-58925732018-04-12 Solution structure of the cytochrome P450 reductase–cytochrome c complex determined by neutron scattering Freeman, Samuel L. Martel, Anne Devos, Juliette M. Basran, Jaswir Raven, Emma L. Roberts, Gordon C. K. J Biol Chem Enzymology 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 on interprotein electron transfer in this system and illustrate a powerful approach for studying solution structures of protein–protein complexes. American Society for Biochemistry and Molecular Biology 2018-04-06 2018-02-23 /pmc/articles/PMC5892573/ /pubmed/29475945 http://dx.doi.org/10.1074/jbc.RA118.001941 Text en © 2018 Freeman et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
spellingShingle Enzymology
Freeman, Samuel L.
Martel, Anne
Devos, Juliette M.
Basran, Jaswir
Raven, Emma L.
Roberts, Gordon C. K.
Solution structure of the cytochrome P450 reductase–cytochrome c complex determined by neutron scattering
title Solution structure of the cytochrome P450 reductase–cytochrome c complex determined by neutron scattering
title_full Solution structure of the cytochrome P450 reductase–cytochrome c complex determined by neutron scattering
title_fullStr Solution structure of the cytochrome P450 reductase–cytochrome c complex determined by neutron scattering
title_full_unstemmed Solution structure of the cytochrome P450 reductase–cytochrome c complex determined by neutron scattering
title_short Solution structure of the cytochrome P450 reductase–cytochrome c complex determined by neutron scattering
title_sort solution structure of the cytochrome p450 reductase–cytochrome c complex determined by neutron scattering
topic Enzymology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892573/
https://www.ncbi.nlm.nih.gov/pubmed/29475945
http://dx.doi.org/10.1074/jbc.RA118.001941
work_keys_str_mv AT freemansamuell solutionstructureofthecytochromep450reductasecytochromeccomplexdeterminedbyneutronscattering
AT martelanne solutionstructureofthecytochromep450reductasecytochromeccomplexdeterminedbyneutronscattering
AT devosjuliettem solutionstructureofthecytochromep450reductasecytochromeccomplexdeterminedbyneutronscattering
AT basranjaswir solutionstructureofthecytochromep450reductasecytochromeccomplexdeterminedbyneutronscattering
AT ravenemmal solutionstructureofthecytochromep450reductasecytochromeccomplexdeterminedbyneutronscattering
AT robertsgordonck solutionstructureofthecytochromep450reductasecytochromeccomplexdeterminedbyneutronscattering