Issue 99, 2016, Issue in Progress

Interactions of the N-terminal domain of human islet amyloid polypeptide with lipid membranes: the effect of cholesterol

Abstract

The 1–19 region of human islet amyloid polypeptide (hIAPP1–19) is a dominating factor causing the interaction between hIAPP and membrane. It contains a short sequence RLANFLV that fulfils the amino-acid arrangement of the inversed cholesterol recognition amino-acid consensus (CARC) and may mediate a direct contact of hIAPP with cholesterol. In this study, we focused on the interaction of hIAPP1–19 with the lipid membrane composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, and examined the role of the CARC motif in the peptide–membrane interaction. Using differential scanning calorimetry, 31P-NMR spectroscopy, 1H-NMR titration measurement and dye leakage assay, we demonstrated that hIAPP1–19 interacts with DPPC vesicles more strongly in the presence of cholesterol than it does in the absence of cholesterol. The peptide–membrane interaction promotes the domain segregation of the raft-containing membrane. The peptide is more disruptive to the cholesterol-containing membrane than it is to the cholesterol-depleted membrane. The substitution of the residue Phe at position 15 of hIAPP1–19 by Leu leads to a distinct decrease in the peptide–membrane interaction in the presence of cholesterol, but the effect of the residue substitution on the peptide–membrane interaction is very small in the absence of cholesterol. The circular dichroism data indicated that a conversion of the structure from a random coil to an α-helix is induced by cholesterol for both peptides and the structural conversion is more Chol-dependent for the wild-type peptide than the F15L variant. Our findings suggest that cholesterol could facilitate the insertion and aggregation of the N-terminal domain of hIAPP in the membrane, and the phenylalanine in the CARC motif could be involved in the interaction of the N-terminal domain with Chol.

Graphical abstract: Interactions of the N-terminal domain of human islet amyloid polypeptide with lipid membranes: the effect of cholesterol

Supplementary files

Article information

Article type
Paper
Submitted
04 Aug 2016
Accepted
01 Oct 2016
First published
03 Oct 2016

RSC Adv., 2016,6, 96837-96846

Interactions of the N-terminal domain of human islet amyloid polypeptide with lipid membranes: the effect of cholesterol

Y. Li, L. Guan, T. Lu, H. Li, Z. Li and F. Li, RSC Adv., 2016, 6, 96837 DOI: 10.1039/C6RA19714K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements