6TF4

Solution structure of RfaH C-terminal domain from Vibrio cholerae

Summary for 6TF4

• Entry DOI: 10.2210/pdb6tf4/pdb
• NMR Information: BMRB: 34450
• Descriptor: Transcription/translation regulatory transformer protein RfaH (1 entity in total)
• Functional Keywords: transcription factor, fold switching, transformer protein, nusg paralog, transcription
• Biological source: Vibrio cholerae
• Total number of polymer chains: 1
• Total formula weight: 7438.49

Authors

Zuber, P.K.,Schweimer, K.,Knauer, S.H. (deposition date: 2019-11-13, release date: 2021-11-24, Last modification date: 2024-06-19)

Primary citation

Zuber, P.K.,Daviter, T.,Heissmann, R.,Persau, U.,Schweimer, K.,Knauer, S.H.
Structural and thermodynamic analyses of the beta-to-alpha transformation in RfaH reveal principles of fold-switching proteins.
Elife, 11:-, 2022

PubMed Abstract: The two-domain protein RfaH, a paralog of the universally conserved NusG/Spt5 transcription factors, is regulated by autoinhibition coupled to the reversible conformational switch of its 60-residue C-terminal Kyrpides, Ouzounis, Woese (KOW) domain between an α-hairpin and a β-barrel. In contrast, NusG/Spt5-KOW domains only occur in the β-barrel state. To understand the principles underlying the drastic fold switch in RfaH, we elucidated the thermodynamic stability and the structural dynamics of two RfaH- and four NusG/Spt5-KOW domains by combining biophysical and structural biology methods. We find that the RfaH-KOW β-barrel is thermodynamically less stable than that of most NusG/Spt5-KOWs and we show that it is in equilibrium with a globally unfolded species, which, strikingly, contains two helical regions that prime the transition toward the α-hairpin. Our results suggest that transiently structured elements in the unfolded conformation might drive the global folding transition in metamorphic proteins in general.

PubMed: 36255050
DOI: 10.7554/eLife.76630

Experimental method

SOLUTION NMR