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

Lauren L. Porter (), Allen K. Kim, Swechha Rimal, Loren L. Looger, Ananya Majumdar, Brett D. Mensh, Mary R. Starich and Marie-Paule Strub
Additional contact information
Lauren L. Porter: National Center for Biotechnology Information, National Institutes of Health
Allen K. Kim: National Center for Biotechnology Information, National Institutes of Health
Swechha Rimal: National Center for Biotechnology Information, National Institutes of Health
Loren L. Looger: Janelia Research Campus
Ananya Majumdar: The Johns Hopkins University Biomolecular NMR Center, The Johns Hopkins University
Brett D. Mensh: Janelia Research Campus
Mary R. Starich: Biochemistry and Biophysics Center, National Institutes of Health
Marie-Paule Strub: Biochemistry and Biophysics Center, National Institutes of Health

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31532-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31532-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31532-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().