Issue 2, 2021

Membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein

Abstract

Understanding of prion aggregation in a membrane environment may help to ameliorate neurodegenerative complications caused by the amyloid forms of prions. Here, we investigated the membrane binding-induced aggregation of yeast prion protein Sup35. Using the combination of fluorescence correlation spectroscopy (FCS) at single molecule resolution and other biophysical studies, we establish that lipid composition and lipid/protein ratio are key modulators of the aggregation kinetics of Sup35. In the presence of a zwitterionic membrane (DMPC), Sup35 exhibited novel biphasic aggregation kinetics at lipid/protein ratios ranging between 20 : 1 and 70 : 1 (termed here as the optimum lipid concentration, OLC). In ratios below (low lipid concentration, LLC) and above (ELC, excess lipid concentration) that range, the aggregation was found to be monophasic. In contrast, in the presence of negatively charged membranes, we did not observe any bi-phasic aggregation kinetics in the entire range of protein to lipid ratios. Our results provide a mechanistic description of the role that membrane concentration/composition-modulated aggregation may play in neurodegenerative diseases.

Graphical abstract: Membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein

Supplementary files

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Article information

Article type
Paper
Submitted
12 11 2020
Accepted
15 1 2021
First published
05 2 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 592-605

Membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein

A. Bandyopadhyay, A. Sannigrahi and K. Chattopadhyay, RSC Chem. Biol., 2021, 2, 592 DOI: 10.1039/D0CB00203H

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