Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
FEBS Lett. 2011 Jan 3;585(1):71-7. doi: 10.1016/j.febslet.2010.11.050. Epub 2010 Dec 3.
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.
在淀粉样蛋白抗性猪胰岛淀粉样多肽 (pIAPP) 序列和淀粉样蛋白倾向人 IAPP (hIAPP) 之间的 10 个变异位点中，有 7 个位于残基 17-29 内，这是 hIAPP 中最具淀粉样蛋白的片段。为了研究这些变异如何影响淀粉样蛋白形成，合成了 26 个 IAPP(17-29)或 IAPP(20-29)变体，并研究了它们的二级结构、淀粉样蛋白形成、寡聚化和细胞毒性。我们的结果表明，与 hIAPP 片段相比，pIAPP 片段不易形成淀粉样蛋白，且细胞毒性明显降低。在 pIAPP(20-29)溶液中观察到一种新的稳定二聚体，而 hIAPP(20-29)主要以单体和三聚体形式存在。在所有人类到猪的取代中，S20R 导致最长的潜伏期，并显著减弱细胞毒性。讨论了 hIAPP 和 pIAPP 片段的不同寡聚化和淀粉样蛋白形成特性。
