STRUCTURAL REQUIREMENTS FOR PROCESSING OF PRO-ADIPOKINETIC HORMONE-I

We found that a seven-residue sequence in pro-adipokinetic hormone I ( proAKH I) which precedes the endopeptidase cleavage site is predicted to form an OMEGA loop. Molecular modelling experiments indicated that a stable OMEGA loop may form at this site, and suggested that loop sta bility may depend on the OMEGA-terminal loop residue, Lys12. The impor tance of this residue in proAKH I processing was confirmed by the obse rvation that replacement of Lys12 by thialysine, a Lys analog with an altered side chain, prevented processing in vivo. In addition we showe d by molecular modelling that this side-chain alteration may prevent f ormation of an OMEGA loop. Together, these approaches lead us to propo se that an OMEGA loop may serve as a recognition motif in proAKH I pro cessing.