Related Experiment Video
Updated: Jul 17, 2026
12:57
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Contact-induced structure transformation in transmembrane prion propagation
1Department of Physics, National Taiwan Normal University, Taipei, Taiwan.
Biophysical Journal
|January 30, 2007
Summary
This study proposes a theoretical model for prion disease's molecular mechanism, suggesting misfolded transmembrane prion protein ((Ctm)PrP) induces misfolding in others. Cooperative dimerization appears crucial in prion disease pathology.
Area of Science:
- Neuroscience
- Biophysics
- Molecular Biology
Background:
- Prion diseases are conformational diseases linked to misfolded prion proteins.
- Transmembrane prion protein ((Ctm)PrP) has been implicated in prion disease transmission.
- Understanding the molecular mechanisms of prion misfolding is critical for disease intervention.
Purpose of the Study:
- To propose a theoretical model for the molecular mechanism of prion diseases.
- To investigate the role of transmembrane prion protein ((Ctm)PrP) misfolding.
- To explore the correlation between folding dynamics and protein concentration.
Main Methods:
- Development of a theoretical model for prion disease molecular mechanisms.
- Utilizing computer simulations to analyze folding time and misfolded (Ctm)PrP concentration.
- Investigating processes like dimerization, trimerization, and cooperative dimerization.
Main Results:
- The study explored the relationship between folding time and misfolded (Ctm)PrP concentration.
- Simulations analyzed various aggregation states including dimerization and trimerization.
- A correlation between incubation time and prion dose in scrapie was compared to simulation data.
Conclusions:
- Cooperative dimerization is proposed as a key factor in the pathological mechanism of prion diseases.
- The theoretical model provides insights into how misfolded (Ctm)PrP propagates.
- Findings suggest potential therapeutic targets related to protein aggregation dynamics.
Related Concept Videos
01:26Insertion of Single-pass Transmembrane Proteins in the RER
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
01:37Energy to Drive Translocation
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
01:34Protein Transport into the Inner Mitochondrial Membrane
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
01:20Cotranslational Protein Translocation
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:21Structure of Porins
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...