Pervasive fold switching in a ubiquitous protein superfamily.

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bioRxiv. 2021 Jun 11;. doi: 10.1101/2021.06.10.447921

Pervasive fold switching in a ubiquitous protein superfamily. Looger Lab

Porter Lauren, Kim Allen, Looger Loren, Majumdar Anaya, Starich Mary

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Abstract

Fold-switching proteins challenge the one-sequence-one-structure paradigm by adopting multiple stable folds. Nevertheless, it is uncertain whether fold switchers are naturally pervasive or rare exceptions to the well-established rule. To address this question, we developed a predictive method and applied it to the NusG superfamily of >15,000 transcription factors. We predicted that a substantial population (25%) of the proteins in this family switch folds. Circular dichroism and nuclear magnetic resonance spectroscopies of 10 sequence-diverse variants confirmed our predictions. Thus, we leveraged family-wide predictions to determine both conserved contacts and taxonomic distributions of fold-switching proteins. Our results indicate that fold switching is pervasive in the NusG superfamily and that the single-fold paradigm significantly biases structure-prediction strategies.

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bioRxiv PrePrint https://doi.org/10.1101/2021.06.10.447921

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Pervasive fold switching in a ubiquitous protein superfamily.

Abstract

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