Related Experiment Video
Updated: Jun 23, 2026
10:08
Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
Preventing amyloid formation by catching unfolded transmembrane segments
H Johansson1, C Nerelius, K Nordling
1Department of Anatomy, Physiology, and Biochemistry, SLU, The Biomedical Center, 75123 Uppsala, Sweden.
Journal of Molecular Biology
|April 21, 2009
Summary
The C-terminal domain (CTC) prevents amyloid fibril formation by binding to nonhelical segments. This chaperone activity extends to Alzheimer's disease-associated amyloid beta-peptide, offering new therapeutic potential.
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Protein misfolding diseases, such as Alzheimer's disease, are linked to beta-sheet amyloid fibril formation.
- Human lung surfactant protein C (SP-C) precursor contains a C-terminal domain (CTC) that inhibits SP-C amyloid fibril formation.
Purpose of the Study:
- To investigate the substrate specificity and anti-amyloid function of the CTC domain.
- To explore the potential of CTC as a therapeutic target for amyloid diseases.
Main Methods:
- Analysis of CTC substrate specificity.
- Testing CTC's anti-amyloid function on different transmembrane segments, including the Alzheimer's disease-associated amyloid beta-peptide.
Main Results:
- CTC binds to all amino acid residues promoting membrane insertion in a nonhelical conformation.
- CTC's anti-amyloid activity extends beyond SP-C to include the amyloid beta-peptide.
- CTC is identified as the first chaperone targeting nonhelical transmembrane segments.
Conclusions:
- CTC exhibits broad substrate specificity for nonhelical transmembrane segments.
- CTC's anti-amyloid function against Alzheimer's disease-related peptides suggests therapeutic potential.
- CTC may be valuable for developing novel diagnostics and anti-amyloid therapies.
Related Concept Videos
03:03Amyloid 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 deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid 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 deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:29Protein Folding Quality Check in the RER
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...
01:32Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
01:37The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...