The Effects of Lipid Membranes, Crowding and Osmolytes on the Aggregation, and Fibrillation Propensity of Human IAPP

Figure 1

Posttranslational modification of hIAPP through the secretory pathway in islet β-cells. Upon expression of the preproIAPP, a disulfide bond is formed at the ER and the N-terminal signal peptide (: MGILKLQVFLIVLSVALNHLKA) is cleaved after transport to the trans-Golgi network. The cleavage of the C-terminus fragment (: NAVEVLKREPLNYLPL) from proIAPP is catalyzed by PC1/3. PC2 removes the N-terminal fragment (: TPIESHQVEKR) of proIAPP within the secretory vesicles. The remaining basic residues at the C-terminus are removed by the action of CPE. The final step of removal of Gly38 and amidation of IAPP at the C-terminus is realized by the PAM complex.