title: Molecular basis for peroxisomal localization of tetrameric carbonyl reductase.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. ntanaka@pharm.showa-u.ac.jp
authors.forename: Nobutada
authors.initials: N
authors.lastname: Tanaka
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Aoki
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ishikura
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagano
authors.forename: Yorishige
authors.initials: Y
authors.lastname: Imamura
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Kazuo T
authors.initials: KT
authors.lastname: Nakamura
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D003067:Coenzymes / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation / Q000235:genetics; D008954:Models, Biological; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D020675:Peroxisomes / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013552:Swine
chemical_list: D003067:Coenzymes; D000429:Alcohol Oxidoreductases