Biological Background

Due to the recent advancement in state-of-art structure determining methodologies, such as cryoEM and solid-state NMR, the interest in full-length amyloid fibril core structures is steadily growing beyond proportion. The atomic details from rapidly accumulating in vitro, as well as in vivo assembled amyloid fibrils are now providing invaluable information on previously undefined properties of amyloid aggregates, such as structural polymorphism, transmissibility patterns, mutation- and species-barriers, cross-interactions with cofactors and many more.

The amount of structures available has far exceeded what it was at the beginning of the 1980s for globular proteins (> 600 structures) which was sufficient to shape the first insights on general principles determining architecture and more fine-graded implications for protein function. Distinct amyloid pathologies are associated to the deposition of specific amyloid conformational variants of the same protein, which have already cultivated the interest to classify them based on disease type and/or levels of intermolecular interactions.

Tau structural polymorphs with diverse cross-sectional architectures are differentially associated to disease-types

Functionality

Database Browsing

Full listing of the database entries
Available sorting selections by alphabetic order by clicking on the browsing table headers (Protein Name, PDB ID, Structure-determining methodology, resolution, disease, author)
Filtering options are available for each browsing table header
Filtering is also available for structures corresponding to specific disease mutations, types and whether or not they derive from in vitro or patient-extracted material
Specific protein entries can be visualised by clicking on a row in the browsing table

Protein Entry Page mode

Protein sequence section

Dynamically highlighted content on disease mutations, experimentally determined aggregation prone regions, and amyloid polymorph lengths

Molecular Graphics Visualisation

Molecular graphic plugin interface that supports viewing of structural polymorphs. It includes multiple visualisation options, such as graphical models (ball-and-stick, ribbon, cartoon representation and more) and colour-coded scaling.

Thermodynamic profiling

Dynamic interface indicating per residue energy contributions on the overall structural stability of user-selected amyloid polymorphs.

User data submission

Amyloid Explorer welcomes active submissions of new fibril structures by the community

Users can submit a novel amyloid fibril structure usign the Submit button on the top-right corner when browsing through the database.

A complete submission form requires the protein name, PDB ID and PDB coordinate file. Upon submission, the data will be manually curated for additional content (disease-mutations, aggregation prone regions) and subjected to automated analysis (thermodynamic profiling using the FoldX force field and cross-correlation analysis using Yasara superpositioning).

For additions to existing entries, user can communicate via amyloid-explorer@switchlab.com

Download options

Description content, as shown in the browsing table, both for user-filtered subsets and unfiltered, can be downloaded in text format using the download option
PDB files of structural polymorphs, both for user-filtered subsets and unfiltered, can be downloaded using the download option
Downloading selections are also available for selected polymorphs through individual protein entry pages

External links

Amyloid Explorer database contains external links to databases with related content on experimentally determined aggregation prone regions

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