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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
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p53 TAD2 Domain (38-61) Forms Amyloid-like Aggregates in Isolation
Kundlik Gadhave1, Shivani K Kapuganti1, Pushpendra Mani Mishra1
1School of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Mandi, Himachal Pradesh 175005, India.
ACS Chemical Neuroscience
|July 20, 2022
Summary
The p53 transactivation domain 2 (TAD2) can aggregate into amyloid-like fibrils. This study isolates and characterizes the aggregation of this specific p53 domain, revealing its inherent tendency to form these structures.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Protein aggregation is linked to neurodegenerative diseases like Alzheimer's and Parkinson's.
- Misfolded and aggregated p53 protein is observed in various cancers.
- While p53 domains are implicated in aggregation, specific subdomains remain unidentified.
Purpose of the Study:
- To investigate the aggregation propensity of the isolated p53 transactivation domain 2 (TAD2) (38-61).
- To characterize the structural features of p53 TAD2 aggregates formed in vitro.
- To understand the role of specific p53 subdomains in protein aggregation.
Main Methods:
- In silico prediction of amyloidogenic tendency.
- In vitro aggregation under acidic pH conditions.
- Characterization using Thioflavin T (ThT) and bis-ANS fluorescence assays.
- Structural analysis via Circular Dichroism (CD) spectroscopy.
- Morphological examination using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM).
Main Results:
- p53 TAD2 domain (38-61) exhibits amyloidogenic properties.
- In vitro aggregation yields characteristic β-sheet-rich amyloid-like fibrils.
- The study successfully isolated and characterized the aggregation of the p53 TAD2 domain.
Conclusions:
- The p53 TAD2 domain (38-61) possesses an intrinsic ability to form amyloid-like aggregates.
- This reductionist approach elucidates the aggregation behavior of a specific p53 subdomain.
- Understanding p53 TAD2 aggregation may offer insights into p53's role in disease pathogenesis.
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