Identification of cytochrome P450 2C2 protein complexes in mouse liver

Research output: Contribution to journalArticle

Abstract

Interactions of microsomal cytochromes P450 (CYPs) with other proteins in the microsomal membrane are important for their function. In addition to their redox partners, CYPs have been reported to interact with other proteins not directly involved in their enzymatic function. In this study, proteins were identified that interact with CYP2C2 in vivo in mouse liver. Flag-tagged CYP2C2 was expressed exogenously in mouse liver and was affinity purified, along with associated proteins which were identified by MS and confirmed by Western blotting. Over 20 proteins reproducibly copurified with CYP2C2. The heterogeneous sedimentation velocity of CYP2C2 and associated proteins by centrifugation in sucrose gradients and sequential immunoprecipitation analysis were consistent with multiple CYP2C2 complexes of differing composition. The abundance of CYPs and other drug metabolizing enzymes and NAD/NADP requiring enzymes associated with CYP2C2 suggest that complexes of these proteins may improve enzymatic efficiency or facilitate sequential metabolic steps. Chaperones, which may be important for maintaining CYP function, and reticulons, endoplasmic reticulum proteins that shape the morphology of the endoplasmic reticulum and are potential endoplasmic reticulum retention proteins for CYPs, were also associated with CYP2C2.

Original languageEnglish (US)
Pages (from-to)3359-3368
Number of pages10
JournalProteomics
Volume11
Issue number16
DOIs
StatePublished - Aug 2011

Keywords

  • Animal proteomics
  • Cytochrome P450
  • Drug-metabolizing enzymes
  • MS
  • Protein-protein interactions
  • Reticulons

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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