Identification of a novel prohormone sorting signal-binding site on carboxypeptidase E, a regulated secretory pathway-sorting receptor.
作者： Chun-Fa Zhang , Christopher R. Snell , Y. Peng Loh
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摘要: Sorting of the prohormone POMC to regulated secretory pathway necessitates binding a sorting signal receptor, identified as membrane carboxypeptidase E (CPE). The signal, located at N terminus consists two acidic (Asp10,Glu14) and hydrophobic (Leu11, Leu18) residues exposed on surface an amphipathic loop. In this study, molecular modeling CPE predicted that in POMC-sorting bind specifically basic residues, Arg255 Lys260, present loop unique CPE, compared with other carboxypeptidases. To test model, these were mutated Ser or Ala, followed by baculovirus expression mutant CPEs Sf9 cells. cell membranes containing mutants either both substituted, showed no of[ 125I]N-POMC1−26 (which contains motif), proinsulin, proenkephalin. contrast, substitution Arg147 Ala147 substra...
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