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Lysophosphatidylcholine modulates the aggregation of human islet amyloid polypeptide
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Xing, Yanting, Pilkington, Emily H., Wang, Miaoyi, Nowell, Cameron J., Kakinen, Aleksandr, Sun, Yunxiang, Wang, Bo, Davis, Thomas P., Ding, Feng and Ke, Pu Chun (2017) Lysophosphatidylcholine modulates the aggregation of human islet amyloid polypeptide. Physical Chemistry Chemical Physics, 19 (45). 30627-30635 . doi:10.1039/C7CP06670H ISSN 1463-9076.
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Official URL: http://dx.doi.org/10.1039/C7CP06670H
Abstract
Amyloid aggregation of human islet amyloid polypeptide (IAPP) is a hallmark of type 2 diabetes (T2D), a metabolic disease and a global epidemic. Although IAPP is synthesized in pancreatic β-cells, its fibrils and plaques are found in the extracellular space indicating a causative transmembrane process. Numerous biophysical studies have revealed that cell membranes as well as model lipid vesicles promote the aggregation of amyloid-β (associated with Alzheimer's), α-synuclein (associated with Parkinson's) and IAPP, through electrostatic and hydrophobic interactions between the proteins/peptides and lipid membranes. Using a thioflavin T kinetic assay, transmission electron microscopy, circular dichroism spectroscopy, discrete molecular dynamics simulations as well as free energy calculations here we show that micellar lysophosphatidylcholine (LPC), the most abundant lysophospholipid in the blood, inhibited the amyloid aggregation of IAPP through nonspecific interactions while elevating the α-helical peptide secondary structure. This surprising finding suggests a native protective mechanism against IAPP aggregation in vivo.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Amyloid, Polypeptides, Lysophospholipids, Non-insulin-dependent diabetes | ||||||||||||||||||
Journal or Publication Title: | Physical Chemistry Chemical Physics | ||||||||||||||||||
Publisher: | Royal Society of Chemistry | ||||||||||||||||||
ISSN: | 1463-9076 | ||||||||||||||||||
Official Date: | 7 December 2017 | ||||||||||||||||||
Dates: |
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Volume: | 19 | ||||||||||||||||||
Number: | 45 | ||||||||||||||||||
Page Range: | 30627-30635 | ||||||||||||||||||
DOI: | 10.1039/C7CP06670H | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||
Date of first compliant deposit: | 16 November 2017 | ||||||||||||||||||
Date of first compliant Open Access: | 1 November 2018 | ||||||||||||||||||
RIOXX Funder/Project Grant: |
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