TY - JOUR
T1 - The role of the disulfide bond in the interaction of islet amyloid polypeptide with membranes
AU - Khemtemourian, L.P.
AU - Engel, M.F.M.
AU - Kruijtzer, J.A.W.
AU - Hoppener, J.W.M.
AU - Liskamp, R.M.J.
AU - Killian, J.A.
PY - 2010
Y1 - 2010
N2 - Human islet amyloid polypeptide (hIAPP)
forms amyloid fibrils in pancreatic islets of patients with
type 2 diabetes mellitus. It has been suggested that the
N-terminal part, which contains a conserved intramolecular
disulfide bond between residues 2 and 7, interacts with
membranes, ultimately leading to membrane damage and
b-cell death. Here, we used variants of the hIAPP1–19
fragment and model membranes of phosphatidylcholine
and phosphatidylserine (7:3, molar ratio) to examine the
role of this disulfide in membrane interactions. We found
that the disulfide bond has a minor effect on membrane
insertion properties and peptide conformational behavior,
as studied by monolayer techniques, 2H NMR, ThT-fluorescence,
membrane leakage, and CD spectroscopy. The
results suggest that the disulfide bond does not play a
significant role in hIAPP–membrane interactions. Hence,
the fact that this bond is conserved is most likely related
exclusively to the biological activity of IAPP as a hormone
AB - Human islet amyloid polypeptide (hIAPP)
forms amyloid fibrils in pancreatic islets of patients with
type 2 diabetes mellitus. It has been suggested that the
N-terminal part, which contains a conserved intramolecular
disulfide bond between residues 2 and 7, interacts with
membranes, ultimately leading to membrane damage and
b-cell death. Here, we used variants of the hIAPP1–19
fragment and model membranes of phosphatidylcholine
and phosphatidylserine (7:3, molar ratio) to examine the
role of this disulfide in membrane interactions. We found
that the disulfide bond has a minor effect on membrane
insertion properties and peptide conformational behavior,
as studied by monolayer techniques, 2H NMR, ThT-fluorescence,
membrane leakage, and CD spectroscopy. The
results suggest that the disulfide bond does not play a
significant role in hIAPP–membrane interactions. Hence,
the fact that this bond is conserved is most likely related
exclusively to the biological activity of IAPP as a hormone
M3 - Article
SN - 0175-7571
VL - 39
SP - 1359
EP - 1364
JO - European Biophysics Journal
JF - European Biophysics Journal
ER -