AlphaFold predicts novel human proteins with knots

The fact that proteins can have their chain formed in a knot is known for almost 30 years. However, as they are not common, only a fraction of such proteins is available in the Protein Data Bank. It was not possible to assess their importance and versatility up until now because we did not have acce...

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Bibliographic Details
Published in:Protein science 2023-05, Vol.32 (5), p.e4631-n/a
Main Authors: Perlinska, Agata P., Niemyska, Wanda H., Gren, Bartosz A., Bukowicki, Marek, Nowakowski, Szymon, Rubach, Pawel, Sulkowska, Joanna I.
Format: Article
Language:English
Subjects:
biological function
Clustering
evolution
folding
Full‐length Paper
Full‐length Papers
Humans
Inspection
Knots
Machine learning
new knotted folds
Protein Conformation
Protein Folding
Protein structure
Proteins
Proteome
Proteomes
Quality assessment
Quality control
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Summary:The fact that proteins can have their chain formed in a knot is known for almost 30 years. However, as they are not common, only a fraction of such proteins is available in the Protein Data Bank. It was not possible to assess their importance and versatility up until now because we did not have access to the whole proteome of an organism, let alone a human one. The arrival of efficient machine learning methods for protein structure prediction, such as AlphaFold and RoseTTaFold, changed that. We analyzed all proteins from the human proteome (over 20,000) determined with AlphaFold in search for knots and found them in less than 2% of the structures. Using a variety of methods, including homolog search, clustering, quality assessment, and visual inspection, we determined the nature of each of the knotted structures and classified it as either knotted, potentially knotted, or an artifact, and deposited all of them in a database available at: https://knotprot.cent.uw.edu.pl/alphafold. Overall, we found 51 credible knotted proteins (0.2% of human proteome). The set of potentially knotted structures includes a new complex type of a knot not reported in proteins yet. That knot type, denoted 63 in mathematical notation, would necessitate a more complex folding path than any knotted protein characterized to date.
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.4631