Non-selective Ion Channel Activity of Polymorphic Human Islet Amyloid Polypeptide (amylin) Double Channels

Overview

Journal Phys Chem Chem Phys

Publisher Royal Society of Chemistry

Specialties Biophysics
Chemistry

Date 2013 Dec 20

PMID 24352606

Citations 17

Authors

Jun Zhao

Rundong Hu

Michele F M Sciacca

Jeffrey R Brender

Hong Chen

Ayyalusamy Ramamoorthy

Jie Zheng

Affiliations

Soon will be listed here.

Abstract

Fundamental understanding of ion channel formation by amyloid peptides, which is strongly linked to cell toxicity, is very critical for (pre)clinical treatment of neurodegenerative diseases. Here, we combine atomistic simulations and experiments to demonstrate a broad range of conformational states of hIAPP double channels in lipid membranes. All individual channels display high selectivity for Cl(-) ions over cations, but the co-existence of polymorphic double channels of different conformations and orientations with different populations determines the non-ionic selectivity nature of the channels, which is different from the typical amyloid-β channels that exhibit Ca(2+) selective ion-permeable characteristics. This work provides a more complete physicochemical mechanism of amyloid-channel-induced toxicity.

Citing Articles

The Effect of Calcium Ions on hIAPP Channel Activity: Possible Implications in T2DM.

Meleleo D, Cibelli G, Valenzano A, Mastrodonato M, Mallamaci R Membranes (Basel). 2023; 13(11).

PMID: 37999364 PMC: 10673357. DOI: 10.3390/membranes13110878.

The role of heat shock proteins in preventing amyloid toxicity.

Torner R, Kupreichyk T, Hoyer W, Boisbouvier J Front Mol Biosci. 2023; 9:1045616.

PMID: 36589244 PMC: 9798239. DOI: 10.3389/fmolb.2022.1045616.

Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas.

Bhowmick D, Kudaibergenova Z, Burnett L, Jeremic A Molecules. 2022; 27(3).

PMID: 35164285 PMC: 8838401. DOI: 10.3390/molecules27031021.

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.

Nguyen P, Ramamoorthy A, Sahoo B, Zheng J, Faller P, Straub J Chem Rev. 2021; 121(4):2545-2647.

PMID: 33543942 PMC: 8836097. DOI: 10.1021/acs.chemrev.0c01122.

Lipid-Chaperone Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins.

Sciacca M, Lolicato F, Tempra C, Scollo F, Sahoo B, Watson M ACS Chem Neurosci. 2020; 11(24):4336-4350.

PMID: 33269918 PMC: 7769131. DOI: 10.1021/acschemneuro.0c00588.

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