Review

Nanopore analysis: An emerging technique for studying the folding and misfolding of proteins

Volume 6, Issue 2   April/May/June 2012
Pages 116 - 123
http://dx.doi.org/10.4161/pri.18665
Keywords: Aβ-peptides, nanopore analysis, prions, protein misfolding, α-synuclein
Authors: Claudia A. Madampage, Omid Tavassoly, Chris Christensen, Meena Kumari and Jeremy S. Lee

View affiliations

Abstract:
Nanopore analysis is an emerging technique that enables the investigation of the conformation of a single peptide or protein molecule. Briefly, a pore is inserted into a membrane under voltage clamp conditions. When a molecule interacts with the pore there is a change in the current, I, for a time, T. Small unfolded molecules can translocate the pore whereas folded or large molecules tend to simply bump into the pore and then diffuse away. Therefore, the parameters, I and T, are dependent on the conformation of the molecule at the instant at which it encounters the pore. Thus, multiple conformations can be detected simultaneously in a single sample. As well, the analysis can be performed under dilute conditions so that folding or dimerization of a peptide can be followed in real time, which is generally difficult to study for proteins that are prone to aggregate. In this report, we describe our initial analysis of (1) Aβ peptides, which are deposited as amyloid plaques in Alzheimer disease, (2) α-synuclein, which is implicated in Parkinson disease and (3) prion proteins whose misfolding is evident in transmissable spongiform encephalopathies. In each case conformational information can be obtained which may help in understanding the early steps in the misfolding pathways.

Received: September 8, 2011; Accepted: November 4, 2011

Preview:



Comments

Please Log In to comment on this article.
If you do not have an account Create One Here.
blog comments powered by Disqus
Advertisements