Lysophosphatidylcholine modulates the aggregation of human islet amyloid polypeptide

Yanting Xing, Emily H. Pilkington, Miaoyi Wang, Cameron J. Nowell, Aleksandr Kakinen, Yunxiang Sun, Bo Wang, Thomas P. Davis, Feng Ding, Pu Chun Ke

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)30627-30635
Number of pages9
JournalPhysical Chemistry Chemical Physics
Volume19
Issue number45
DOIs
Publication statusPublished - 7 Dec 2017

Cite this

Xing, Yanting ; Pilkington, Emily H. ; Wang, Miaoyi ; Nowell, Cameron J. ; Kakinen, Aleksandr ; Sun, Yunxiang ; Wang, Bo ; Davis, Thomas P. ; Ding, Feng ; Ke, Pu Chun. / Lysophosphatidylcholine modulates the aggregation of human islet amyloid polypeptide. In: Physical Chemistry Chemical Physics. 2017 ; Vol. 19, No. 45. pp. 30627-30635.
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Lysophosphatidylcholine modulates the aggregation of human islet amyloid polypeptide. / Xing, Yanting; Pilkington, Emily H.; Wang, Miaoyi; Nowell, Cameron J.; Kakinen, Aleksandr; Sun, Yunxiang; Wang, Bo; Davis, Thomas P.; Ding, Feng; Ke, Pu Chun.

In: Physical Chemistry Chemical Physics, Vol. 19, No. 45, 07.12.2017, p. 30627-30635.

Research output: Contribution to journalArticleResearchpeer-review

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