Difference between revisions of "Part:BBa K4165181"

Revision as of 17:36, 10 October 2022

Amyloid beta peptide 1 (R5)

This part encodes Amyloid 𝛽 seed (37-42) which has the ability to bind to A𝛽 plaques inside the brain.

Usage and Biology

Arginine (R) is a basic amino acid with the presence of a guanidino group at its aliphatic side chain. It is typically protonated at physiological pH where the guanidino group turns into a cationic guanidinium moiety that is highly stable and able to self-associate and cluster. These properties contribute to the intra- and intermolecular associations of arginine residues, as it provides a great capacity for electrostatic interactions (especially hydrogen-bonding) that results in a tendency to form stable clusters in solution.

Arginine has long been recognized as a chemical chaperone, with its ability to interact with and influence proteins in solution. In silico experiments have proved its ability to bind protein surfaces for a long time through its carboxyl and guanidinium groups, and form clusters through self-association with other arginine molecules. This has led to various in vitro experiments that proved the ability of arginine to suppress protein aggregations, which made it a very interesting candidate in the modulation of proteopathies correlated with Alzheimer’s disease.

Polyarginine peptides have different mechanisms in cytotoxicity modulation of amyloid beta aggregates, R5 peptide modulates AB aggregation by directing the formation of large, amorphous, non-toxic aggregates, as it changes the aggregate conformation by electrostatically stabilizing monomers that favor non-oligomeric aggregation pathways.

Sequence and Features

Dry Lab Characterization

Modeling

For the prediction of 3D structure, the peptide was modeled through three peptide modeling software (Apptest, Alphafold2, and Pepfold3) followed by ranking them according to our pipeline parameters. Various models for this peptide ranked 6 out of 6, with the top-ranked model being (Alphafold model 1).

                                Figure 1.: Predicted 3D structure of R5 peptide.

Functional Parameters

Overall charge: +5.0

References

Mamsa, S. S., & Meloni, B. P. (2021). Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease. Frontiers in Molecular Neuroscience. https://doi.org/10.3389/fnmol.2021.759729