STEROIDS, FATTY ACYL-COA, AND STEROLS ARE SUBSTRATES OF 80-KDA MULTIFUNCTIONAL PROTEIN

The 2.9-kb mRNA of 17 beta-hydroxysteroid dehydrogenase IV codes for a n 80-kDa (737 amino acids) protein featuring domains that are not pres ent in the other human 17 beta-hydroxysteroid dehydrogenases. The N-te rminal part reveals conserved motifs of the short-chain alcohol dehydr ogenase family. The central- and C-terminal domains are similar to per oxisomal enzymes for beta-oxidation of fatty acids and to sterol carri er protein 2. The 80-kDa protein is N-terminally cleaved to a 32-kDa f ragment (amino acids 1-323). Both the 80-kDa and the N-terminal 32-kDA peptides are able to catalyze the dehydrogenation with steroids at th e C17 position and with 3-hydroxyacyl-CoA. The central part of the 80- kDa protein (amino acids 324-596) catalyzes the 2-enoyl-acyl-Coa hydra tase reaction with high efficiency. The C-terminal part of the 80-kDa protein (amino acids 597-737) facilitates the transfer of 7-dehydrocho lesterol and phosphatidylcholine between membranes in vitro. The uniqu e multidomain structure of the 80-kDa protein permits the catalysis of several reactions previously thought to be performed by complexes of different enzymes. (C) 1997 by Elsevier Science Inc.