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Predictable fold switching by the SARS-CoV-2 protein ORF9b.

ABSTRACT: Extant fold-switching proteins remodel their secondary structures and change their functions in response to environmental stimuli. These shapeshifting proteins regulate biological processes and are associated with a number of diseases, including tuberculosis, cancer, Alzheimer's, and autoimmune disorders. Thus, predictive methods are needed to identify more fold-switching proteins, especially since all naturally occurring instances have been discovered by chance. In response to this need, two high-throughput predictive methods have recently been developed. Here we test them on ORF9b, a newly discovered fold switcher and potential therapeutic target from the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Promisingly, both methods correctly indicate that ORF9b switches folds. We then tested the same two methods on ORF9b1, the ORF9b homolog from SARS-CoV-1. Again, both methods predict that ORF9b1 switches folds, a finding consistent with experimental binding studies. Together, these results (a) demonstrate that protein fold switching can be predicted using high-throughput computational approaches and (b) suggest that fold switching might be a general characteristic of ORF9b homologs.

SUBMITTER: Porter LL

PROVIDER: S-EPMC8242659 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Predictable fold switching by the SARS-CoV-2 protein ORF9b.

Porter Lauren L LL

Protein science : a publication of the Protein Society 20210510 8

Extant fold-switching proteins remodel their secondary structures and change their functions in response to environmental stimuli. These shapeshifting proteins regulate biological processes and are associated with a number of diseases, including tuberculosis, cancer, Alzheimer's, and autoimmune disorders. Thus, predictive methods are needed to identify more fold-switching proteins, especially since all naturally occurring instances have been discovered by chance. In response to this need, two hi ...[more]

PMID: 33934422

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Dataset Information

Predictable fold switching by the SARS-CoV-2 protein ORF9b.

Publications

Predictable fold switching by the SARS-CoV-2 protein ORF9b.

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