TY - JOUR
T1 - Cyclic N-terminal loop of amylin forms non amyloid fibers
AU - Cope, Stephanie M.
AU - Shinde, Sandip
AU - Best, Robert B.
AU - Ghirlanda, Giovanna
AU - Vaiana, Sara M.
N1 - Funding Information:
This work was supported by ASU start-up funds to S.M.V. G.G. and S.S. were supported in part by National Science Foundation CAREER award 0449842. R.B.B. was supported by a Royal Society University Research Fellowship and by the Intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH).
PY - 2013/10/1
Y1 - 2013/10/1
N2 - We report for the first time, to our knowledge, that the N-terminal loop (N-loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) forms extremely long and stable non-β-sheet fibers in solution under the same conditions in which human amylin (hIAPP) forms amyloid fibers. This observation applies to the cyclic, oxidized form of the N-loop but not to the linear, reduced form, which does not form fibers. Our findings indicate a potential role of direct N-loop-N-loop interactions in hIAPP aggregation, which has not been previously explored, with important implications for the mechanism of hIAPP amyloid fiber formation, the inhibitory action of IAPP variants, and the competition between ordered and disordered aggregation in peptides of the calcitonin peptide family.
AB - We report for the first time, to our knowledge, that the N-terminal loop (N-loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) forms extremely long and stable non-β-sheet fibers in solution under the same conditions in which human amylin (hIAPP) forms amyloid fibers. This observation applies to the cyclic, oxidized form of the N-loop but not to the linear, reduced form, which does not form fibers. Our findings indicate a potential role of direct N-loop-N-loop interactions in hIAPP aggregation, which has not been previously explored, with important implications for the mechanism of hIAPP amyloid fiber formation, the inhibitory action of IAPP variants, and the competition between ordered and disordered aggregation in peptides of the calcitonin peptide family.
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U2 - 10.1016/j.bpj.2013.08.026
DO - 10.1016/j.bpj.2013.08.026
M3 - Article
C2 - 24094407
AN - SCOPUS:84885129449
VL - 105
SP - 1661
EP - 1669
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 7
ER -