Related Experiment Video
Updated: Mar 18, 2026
10:08
Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
12.3K
Intramolecular diffusion controls aggregation of the PAPf39 peptide
Kinshuk R Srivastava1, Kinsley C French2, Franco O Tzul2
1Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824, USA.
Biophysical Chemistry
|July 10, 2016
Summary
Human prostatic acidic phosphatase (PAP) peptide dynamics influence fibril formation. Understanding peptide reconfiguration rates is key to modeling early-stage protein aggregation and oligomerization.
Area of Science:
- Biochemistry
- Biophysics
- Protein Chemistry
Background:
- Human prostatic acidic phosphatase (PAP) is a protein fragment found in semen.
- This PAP fragment (39 residues) readily forms amyloid-like fibrils.
- Fibrillization accelerates upon deleting the first 8 charged residues, suggesting peptide dynamics are crucial.
Purpose of the Study:
- To investigate the hypothesis that peptide dynamics control fibrillization.
- To correlate intramolecular diffusion rates with fibrillization kinetics.
- To elucidate the early stages of PAP peptide aggregation.
Main Methods:
- Measurement of intramolecular diffusion for full-length and 8-residue deletion PAP peptides.
- Experiments conducted at two different pH values.
- Analysis using a kinetic model for early-stage aggregation.
Main Results:
- A direct correlation was observed between intramolecular diffusion rates and fibrillization lag times.
- Peptide dynamics, specifically reconfiguration rates, were found to influence aggregation.
- The pH-dependent dynamics of the peptides impact their fibrillization propensity.
Conclusions:
- Peptide reconfiguration dynamics are critical for controlling the rate of PAP fibril formation.
- A kinetic model explains early aggregation where oligomerization depends on peptide reconfiguration.
- These findings provide insights into the molecular mechanisms of amyloid formation in PAP peptides.
Related Concept Videos
01:24Protein Diffusion in the Membrane
6.1K
Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
6.1K
01:25Protein Folding
12.1K
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...
12.1K
03:03Amyloid Fibrils
12.8K
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,...
12.8K
01:19Translocation of Proteins into the Mitochondria
13.6K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.6K
01:32Pinching-off of Coated Vesicles
4.4K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
4.4K
03:00Molecular Chaperones and Protein Folding
20.7K
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...
20.7K