Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

作者：Zhang, Xin; Cheng, Biao; Gong, Hao; Li, Chuanzhou; Chen, Hong; Zheng, Ling^*; Huang, Kun

来源：FEBS LETTERS, 2011, 585(1): 71-77.

DOI：10.1016/j.febslet.2010.11.050

• Amylin
• Amyloid fibril
• IAPP
• Oligomerization
• Seeding
• Type 2 diabetes mellitus

Of 10 variation sites between sequences of amyloid-resistant porcine islet amyloid polypeptide (pIAPP) and amyloid-prone human IAPP (hIAPP), seven locate within residues 17-29, the most amyloidogenic fragment within hIAPP. To investigate how these variations affect amyloidogenicity, 26 IAPP(17-29) or IAPP(20-29) variants were synthesized and their secondary structures, amyloidogenicity, oligomerization and cytotoxicity were studied. Our results indicated that pIAPP fragments are refractory to amyloid formation and significantly less cytotoxic compared with hIAPP fragments. A novel stable dimer was observed in pIAPP(20-29) solution, whereas hIAPP(20-29) exists mostly as monomers and trimers. Among all human to porcine substitutions, S20R caused the most prolonged lag time and significantly attenuated cytotoxicity. The different oligomerization and amyloidogenic properties of hIAPP and pIAPP fragments are discussed. @@@ Structured summary: @@@ pIAPP and pIAPP bind: shown by molecular sieving (view

• 出版日期2011-1-3
• 单位华中科技大学; 武汉大学