Related Experiment Video
Updated: Nov 1, 2025
08:33
Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
Published on: March 24, 2019
7.7K
Moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) modulates protein aggregation
Surbhi Chaudhary1, Asmita Dhiman1, Anil Patidar1
1Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India.
Summary
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents protein aggregation by interacting with misfolded cytosolic prion (cyPrP) and huntingtin (httQ-103). Overexpressing GAPDH reduces detectable protein aggregates, highlighting its role in maintaining protein solubility.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Protein misfolding and aggregation are linked to cellular dysfunction and disease.
- The cellular machinery normally prevents aggregation, but failures lead to pathological states.
- Cytosolic prion (cyPrP) and huntingtin (httQ-103) are aggregation-prone proteins implicated in neurodegenerative diseases.
Purpose of the Study:
- To investigate the interaction between aggregation-prone proteins and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
- To determine if GAPDH influences the aggregation state of cyPrP and httQ-103.
- To elucidate the role of GAPDH in cellular protein homeostasis.
Main Methods:
- Förster Resonance Energy Transfer (FRET) based analysis.
- Biochemical assays to detect protein aggregation.
- Cellular overexpression of GAPDH.
Main Results:
- FRET and biochemical data show that cyPrP and httQ-103 interact with GAPDH.
- Overexpression of GAPDH significantly reduces the formation of detectable protein aggregates.
- GAPDH demonstrates a protective effect against the aggregation of heterogeneous proteins.
Conclusions:
- GAPDH actively participates in shielding and maintaining the solubility of aggregation-prone proteins like cyPrP and httQ-103.
- This abundant cytoplasmic protein plays a crucial role in cellular protein quality control.
- Targeting GAPDH function may offer therapeutic strategies for protein aggregation diseases.
Related Concept Videos
02:04Covalently Linked Protein Regulators
8.1K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.1K
03:03Amyloid Fibrils
10.9K
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,...
10.9K
01:29Protein Folding Quality Check in the RER
4.5K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
4.5K
02:58Regulated Protein Degradation
8.0K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.0K
02:58Regulated Protein Degradation
2.8K
2.8K