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The protein partners of GTP cyclohydrolase I in rat organs. PLoS One 2012;7(3):e33991

Date

04/06/2012

Pubmed ID

22479495

Pubmed Central ID

PMC3313957

DOI

10.1371/journal.pone.0033991

Abstract

OBJECTIVE: GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The endogenous GCH1-interacting partners have not been identified. Here, we determined endogenous GCH1-interacting proteins in rat.

METHODS AND RESULTS: A pulldown and proteomics approach were used to identify GCH1 interacting proteins in rat liver, brain, heart and kidney. We demonstrated that GCH1 interacts with at least 17 proteins including GTP cyclohydrolase I feedback regulatory protein (GFRP) in rat liver by affinity purification followed by proteomics and validated six protein partners in liver, brain, heart and kidney by immunoblotting. GCH1 interacts with GFRP and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I (EIF3I) in all organs tested. Furthermore, GCH1 associates with mitochondrial proteins and GCH1 itself locates in mitochondria.

CONCLUSION: GCH1 interacts with proteins in an organ dependant manner and EIF3I might be a general regulator of GCH1. Our finding indicates GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis.

Author List

Du J, Teng RJ, Lawrence M, Guan T, Xu H, Ge Y, Shi Y

Author

Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acyl-CoA Dehydrogenase, Long-Chain
Animals
Cell Line
Eukaryotic Initiation Factor-3
GTP Cyclohydrolase
Humans
Liver
Male
Mitochondria
Multiprotein Complexes
Protein Binding
Protein Interaction Mapping
Protein Transport
Proteins
Rats
Rats, Sprague-Dawley
Reproducibility of Results
Retinal Dehydrogenase
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75