Related Experiment Video
Updated: Aug 9, 2025
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
18.5K
DJ-1 Molecular Chaperone Activity Depresses Tau Aggregation Propensity through Interaction with Monomers
Daniela Jimenez-Harrison1, Carol J Huseby2, Claire N Hoffman2
1Medical Scientist Training Program, The Ohio State University, Columbus, Ohio 43210, United States.
Biochemistry
|February 22, 2023
Summary
The molecular chaperone DJ-1 acts as a holdase, inhibiting tau protein aggregation in neurodegenerative diseases. This interaction suggests DJ-1
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Tau aggregates are key pathological markers in tauopathies like Alzheimer's disease.
- The molecular chaperone DJ-1 is found with tau pathology, but its functional role is unclear.
Purpose of the Study:
- To investigate the functional link between tau and DJ-1 interactions.
- To determine DJ-1's effect on tau aggregation in vitro.
Main Methods:
- In vitro studies of full-length 2N4R tau and wild-type/mutant DJ-1 under aggregation-promoting conditions.
- Assessing DJ-1's direct binding to tau's microtubule-binding repeat region.
- Evaluating the impact of DJ-1 on tau seeding activity in a biosensor cell model.
Main Results:
- DJ-1 inhibited tau filament formation in a concentration-dependent manner.
- DJ-1's tau chaperone activity was reduced by Parkinson's disease-associated mutations (M26I, E64D).
- DJ-1 directly bound tau but did not reduce the seeding activity of preformed tau seeds.
Conclusions:
- DJ-1 functions as a holdase chaperone for tau, similar to its role with alpha-synuclein.
- DJ-1 may be part of an endogenous defense system against the aggregation of intrinsically disordered proteins like tau.
Related Concept Videos
03:00Molecular Chaperones and Protein Folding
18.1K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.1K
03:03Amyloid Fibrils
9.7K
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,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.7K
01:26Bacterial Protein Maturation
50
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
50