Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1661-1669 |
| Number of pages | 9 |
| Journal | Biophysical Journal |
| Volume | 105 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Oct 1 2013 |
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ASJC Scopus subject areas
- Biophysics
Cite this
Cyclic N-terminal loop of amylin forms non amyloid fibers. / Cope, Stephanie M.; Shinde, Sandip; Best, Robert B.; Ghirlanda, Giovanna; Vaiana, Sara M.
In: Biophysical Journal, Vol. 105, No. 7, 01.10.2013, p. 1661-1669.Research output: Contribution to journal › Article
}
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84885129449&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885129449&partnerID=8YFLogxK
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 -