Molecular Basis for Peroxisomal Localization of Tetrameric Carbonyl Reductase

• Published in: Structure (London) Vol. 16; no. 3; pp. 388 - 397
• Main Authors: Tanaka, Nobutada, Aoki, Ken-ichi, Ishikura, Shuhei, Nagano, Makoto, Imamura, Yorishige, Hara, Akira, Nakamura, Kazuo T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2008
• Subjects: Alcohol Oxidoreductases - chemistry; Alcohol Oxidoreductases - genetics; Alcohol Oxidoreductases - metabolism; Amino Acid Motifs - genetics; Animals; Binding Sites - genetics; Carbonyls; CELLBIO; Coenzymes - metabolism; Crystal structure; Dimerization; Enzyme Activation - genetics; Localization; Mathematical analysis; MICROBIO; Models, Biological; Models, Molecular; Mutagenesis, Site-Directed; Mutation; Peroxisomes - metabolism; Position (location); Protein Binding; Protein Structure, Quaternary; Protein Structure, Tertiary; Protein Transport; Recognition; Reductases; Swine; Vectors (mathematics); CELLBIO; MICROBIO
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2007.12.022

Pig heart peroxisomal carbonyl reductase (PerCR) belongs to the short-chain dehydrogenase/reductase family, and its sequence comprises a C-terminal SRL tripeptide, which is a variant of the type 1 peroxisomal targeting signal (PTS1) Ser-Lys-Leu. PerCR is imported into peroxisomes of HeLa cells when the cells are transfected with vectors expressing the enzyme. However, PerCR does not show specific targeting when introduced into the cells with a protein transfection reagent. To understand the structural basis for peroxisomal localization of PerCR, we determined the crystal structure of PerCR. Our data revealed that the C-terminal PTS1 of each subunit of PerCR was involved in intersubunit interactions and was buried in the interior of the tetrameric molecule. These findings indicate that the PTS1 receptor Pex5p in the cytosol recognizes the monomeric form of PerCR whose C-terminal PTS1 is exposed, and that this PerCR is targeted into the peroxisome, thereby forming a tetramer.