The amyloid conformation is considered a fundamental state of proteins and the propensity to populate it
a generic property of polypeptides. Multiple proteome-wide analyses addressed the presence of amyloidogenic
regions in proteins, nurturing our understanding of their nature and biological implications.
However, these analyses focused on highly aggregation-prone and hydrophobic stretches that are only marginally found in intrinsically disordered regions (IDRs).
We have recently explored the prevalence of cryptic amyloidogenic regions (CARs) of polar nature in IDRs using the Waltz algorithm, a well-validated amyloid predictor, by making the amyloid threshold less stringent (85, 80 and 73.5) to cover the amyloid propensities ranging between the minimum required for polar amyloid identification (73.5) and the one established for conventional amyloids (92, or 'Best Overall Performance').
CARs are widespread in IDRs and associated with IDPs function, with particular involvement in protein–protein interactions, but their presence is also connected to a risk of malfunction. By exploring this function/malfunction dichotomy, we speculated that ancestral CARs might have evolved into functional interacting regions playing a significant role in protein evolution at the origins of life.
Under the section 'Database', users can search for any disordered protein of interest at the desired Waltz threshold (85, 80 or 73.5). Different identifiers such as DisProt ID, UniProt ID, protein name, organism or sequence can be used to query any possible CAR. If a match is detected, detailed information about each CAR will appear on the screen. That includes the starting and ending position of the specific CARrelative to the entire protein sequence, along with its length, amino acidic sequence and Waltz score.
Please be aware that only IDRs longer than 20 amino acids have been considered. In addition, only positively detected regions consisting of at least 7 residues are considered as CARs.
To access additional disorder features about all described CARs or perform further analyses, we recommend users to download the data in the desired format, which are freely available under the 'Download' section of the server. In the provided files, all entries include complementary DisProt information about the nature of the disordered region.
The numbers embedding the CARs-DB can be visualized under the 'Statistics' section of the site. In there you will find interactive graphics about the CARs' abundance and distribution to easily oversee the organization of the database.