Porcine islet amyloid polypeptide fragments are refractory to amyloid formation.
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.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Xin
X
Zhang
Biao
B
Cheng
Hao
H
Gong
Chuanzhou
C
Li
Hong
H
Chen
Ling
L
Zheng
Kun
K
Huang
D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D055503:Protein Multimerization; D013552:Swine
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments