Journal
FEBS LETTERS
Volume 585, Issue 1, Pages 71-77Publisher
WILEY
DOI: 10.1016/j.febslet.2010.11.050
Keywords
Amylin; Amyloid fibril; IAPP; Oligomerization; Seeding; Type 2 diabetes mellitus
Funding
- Natural Science Foundation of China [30801445, 30970607, 30870949]
- National Basic Research Program of China [2009CB918304]
- Program for New Century Excellent Talents in University [NECT-10-0623]
- Chinese Ministry of Education [109103]
- Fundamental Research Funds for the Central Universities
- Important National Science and Technology Specific Projects [2009ZX09301-014]
Ask authors/readers for more resources
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 interactions 1, 2) hIAPP and hIAPP bind: shown by molecular sieving (view interactions 1, 2) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available