TY  - JOUR
AU  - Poojari, Chetan
AU  - Xiao, D.
AU  - Batista, V. S.
AU  - Strodel, Birgit
TI  - Membrane Permeation Induced by Aggregates of Human Islet Amyloid Polypeptides
JO  - Biophysical journal
VL  - 105
SN  - 0006-3495
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - FZJ-2013-05968
SP  - 2323-2332
PY  - 2013
AB  - Several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases as well as nonneuropathic diseases such as type II diabetes and atrial amyloidosis are associated with aggregation of amyloid polypeptides into fibrillar structures, or plaques. In this study, we use molecular dynamics simulations to test the stability and orientation of membrane-embedded aggregates of the human islet amyloid polypeptide (hIAPP) implicated in type II diabetes. We find that in both monolayers and bilayers of dipalmitoylphosphatidylglycerol (DPPG) hIAPP trimers and tetramers remain inside the membranes and preserve their β-sheet secondary structure. Lipid bilayer-inserted hIAPP trimers and tetramers orient inside DPPG at 60° relative to the membrane/water interface and lead to water permeation and Na+ intrusion, consistent with ion-toxicity in islet β-cells. In particular, hIAPP trimers form a water-filled β-sandwich that induce water permeability comparable with channel-forming proteins, such as aquaporins and gramicidin-A. The predicted disruptive orientation is consistent with the amphiphilic properties of the hIAPP aggregates and could be probed by chiral sum frequency generation (SFG) spectroscopy, as predicted by the simulated SFG spectra.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000327285100013
C6  - pmid:24268144
DO  - DOI:10.1016/j.bpj.2013.09.045
UR  - https://juser.fz-juelich.de/record/140001
ER  -