[feed] Atom [feed] RSS 1.0 [feed] RSS 2.0

Scott J , Alistair and Kozhinjampara R , Mahendran (2021) Constructing ion channels from water-soluble α-helical barrels. Nature chemistry, 13 (7). pp. 643-650. ISSN 1755-4349

[img]
Preview
Text
Constructing ion.pdf

Download (1948Kb) | Preview

Abstract

The design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide-lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble α-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These α-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide.

Item Type: Article
Subjects: Membrane Biology
Depositing User: Central Library RGCB
Date Deposited: 28 Sep 2021 06:14
Last Modified: 28 Sep 2021 06:14
URI: http://rgcb.sciencecentral.in/id/eprint/1040

Actions (login required)

View Item View Item