Many dissimilar NusG protein domains switch between α-helix and β-sheet folds.

Autor: Porter, Lauren L., Kim, Allen K., Rimal, Swechha, Looger, Loren L., Majumdar, Ananya, Mensh, Brett D., Starich, Mary R., Strub, Marie-Paule
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Zdroj: Nature Communications; 7/1/2022, Vol. 13 Issue 1, p1-12, 12p
Abstrakt: Folded proteins are assumed to be built upon fixed scaffolds of secondary structure, α-helices and β-sheets. Experimentally determined structures of >58,000 non-redundant proteins support this assumption, though it has recently been challenged by ~100 fold-switching proteins. Though ostensibly rare, these proteins raise the question of how many uncharacterized proteins have shapeshifting–rather than fixed–secondary structures. Here, we use a comparative sequence-based approach to predict fold switching in the universally conserved NusG transcription factor family, one member of which has a 50-residue regulatory subunit experimentally shown to switch between α-helical and β-sheet folds. Our approach predicts that 24% of sequences in this family undergo similar α-helix ⇌ β-sheet transitions. While these predictions cannot be reproduced by other state-of-the-art computational methods, they are confirmed by circular dichroism and nuclear magnetic resonance spectroscopy for 10 out of 10 sequence-diverse variants. This work suggests that fold switching may be a pervasive mechanism of transcriptional regulation in all kingdoms of life. Folded proteins are composed of secondary structures, α-helices and β-sheets, that are generally assumed to be stable. Here, the authors combine computational prediction with experimental validation to show that many sequence-diverse NusG protein domains switch completely from α-helix to β-sheet folds. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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