Dataset Information

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

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) A? peptides, which are deposited as amyloid plaques in Alzheimer disease, (2) ?-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.

SUBMITTER: Madampage C

PROVIDER: S-EPMC7082088 | biostudies-literature | 2012 Apr-Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Madampage Claudia C Tavassoly Omid O Christensen Chris C Kumari Meena M Lee Jeremy S JS

Prion 20120401 2

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 ...[more]

PMID: 22421211

Similar Datasets

Project description:We describe here an algorithm for distinguishing sequential from nonsequentially folding proteins. Several experiments have recently suggested that most of the proteins that are synthesized in the eukaryotic cell may fold sequentially. This proposed folding mechanism in vivo is particularly advantageous to the organism. In the absence of chaperones, the probability that a sequentially folding protein will misfold is reduced significantly. The problem we address here is devising a procedure that would differentiate between the two types of folding patterns. Footprints of sequential folding may be found in structures where consecutive fragments of the chain interact with each other. In such cases, the folding complexity may be viewed as being lower. On the other hand, higher folding complexity suggests that at least a portion of the polypeptide backbone folds back upon itself to form three-dimensional (3D) interactions with noncontiguous portion(s) of the chain. Hence, we look at the mechanism of folding of the molecule via analysis of its complexity, that is, through the 3D interactions formed by contiguous segments on the polypeptide chain. To computationally splice the structure into consecutively interacting fragments, we either cut it into compact hydrophobic folding units or into a set of hypothetical, transient, highly populated, contiguous fragments ("building blocks" of the structure). In sequential folding, successive building blocks interact with each other from the amino to the carboxy terminus of the polypeptide chain. Consequently, the results of the parsing differentiate between sequentially vs. nonsequentially folded chains. The automated assessment of the folding complexity provides insight into both the likelihood of misfolding and the kinetic folding rate of the given protein. In terms of the funnel free energy landscape theory, a protein that truly follows the mechanism of sequential folding, in principle, encounters smoother free energy barriers. A simple sequentially folded protein should, therefore, be less error prone and fold faster than a protein with a complex folding pattern.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets