Uncovering new families and folds in the natural protein universe

Durairaj, Janani and Waterhouse, Andrew M. and Mets, Toomas and Brodiazhenko, Tetiana and Abdullah, Minhal and Studer, Gabriel and Tauriello, Gerardo and Akdel, Mehmet and Andreeva, Antonina and Bateman, Alex and Tenson, Tanel and Hauryliuk, Vasili and Schwede, Torsten and Pereira, Joana. (2023) Uncovering new families and folds in the natural protein universe. Nature, 622 (7983). pp. 646-653.

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Official URL: https://edoc.unibas.ch/95694/

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We are now entering a new era in protein sequence and structure annotation, with hundreds of millions of predicted protein structures made available through the AlphaFold database; 1; . These models cover nearly all proteins that are known, including those challenging to annotate for function or putative biological role using standard homology-based approaches. In this study, we examine the extent to which the AlphaFold database has structurally illuminated this "dark matter" of the natural protein universe at high predicted accuracy. We further describe the protein diversity that these models cover as an annotated interactive sequence similarity network, accessible at https://uniprot3d.org/atlas/AFDB90v4 . By searching for novelties from sequence, structure, and semantic perspectives, we uncovered the β-flower fold, added multiple protein families to Pfam database; 2; , and experimentally demonstrate that one of these belongs to a new superfamily of translation-targeting toxin-antitoxin systems, TumE-TumA. This work underscores the value of large-scale efforts in identifying, annotating, and prioritising novel protein families. By leveraging the recent deep learning revolution in protein bioinformatics, we can now shed light into uncharted areas of the protein universe at an unprecedented scale, paving the way to innovations in life sciences and biotechnology.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)
UniBasel Contributors:Schwede, Torsten and Soares Pereira, Joana Maria and Waterhouse, Andrew and Studer, Gabriel and Durairaj, Janani
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 Oct 2023 08:22
Deposited On:24 Oct 2023 08:19

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