Related Experiment Video

Updated: Jun 3, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

Aberrant protein interactions in amyloid disease

R Martin Vabulas, F Ulrich Hartl

    Cell Cycle (Georgetown, Tex.)
    |April 6, 2011
    PubMed

    Insights

    Protein aggregation causes cell damage by trapping essential proteins. This study reveals how metastable proteins, crucial for cell functions, are vulnerable to sequestration by amyloid-like aggregates, leading to severe toxicity.

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Background:

    • The precise mechanisms linking protein aggregation to cellular toxicity and disease remain incompletely understood.
    • Amyloid-like protein aggregation is implicated in various neurodegenerative disorders.

    Discussion:

    • Artificial beta-sheet proteins were used to model amyloid-like aggregation.
    • Quantitative proteomics identified specific protein vulnerabilities within the cellular network.

    Key Insights:

    • Metastable proteins, often large and unstructured, are preferentially sequestered by aggregates.
    • These vulnerable proteins function as critical network hubs involved in transcription, translation, trafficking, and cytoskeletal organization.
    • Co-aggregation of these essential proteins contributes significantly to the multi-factorial toxicity observed in intracellular amyloidogenesis.

    Outlook:

    • Further research can elucidate the precise structural features of metastable proteins that confer aggregation susceptibility.
    • Understanding these interactions may lead to novel therapeutic strategies targeting protein aggregation diseases.
    • This model system provides a platform for investigating the broader impact of protein aggregation on cellular networks.

    More Related Videos

    Biochemical Purification and Proteomic Characterization of Amyloid Fibril Cores from the Brain09:00

    Biochemical Purification and Proteomic Characterization of Amyloid Fibril Cores from the Brain

    Published on: April 28, 2022

    Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy06:27

    Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy

    Published on: November 30, 2018

    Related Concept Videos

    Amyloid Fibrils03:03

    Amyloid Fibrils

    Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
    Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
    Amyloid Fibrils03:03

    Amyloid Fibrils

    Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
    Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
    Alzheimer Disease ll: Pathophysiology01:23

    Alzheimer Disease ll: Pathophysiology

    Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
    Factors Affecting Protein-Drug Binding: Drug Interactions01:23

    Factors Affecting Protein-Drug Binding: Drug Interactions

    Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
    Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
    Protein Networks02:26

    Protein Networks

    An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
    These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
    Protein-protein Interfaces02:04

    Protein-protein Interfaces

    Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...