6tf4

Publication Abstract from PubMed

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 alpha-hairpin and a beta-barrel. In contrast, NusG/Spt5-KOW domains only occur in the beta-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 beta-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 alpha-hairpin. Our results suggest that transiently structured elements in the unfolded conformation might drive the global folding transition in metamorphic proteins in general.

Structural and thermodynamic analyses of the beta-to-alpha transformation in RfaH reveal principles of fold-switching proteins.,Zuber PK, Daviter T, Heissmann R, Persau U, Schweimer K, Knauer SH Elife. 2022 Oct 18;11:e76630. doi: 10.7554/eLife.76630. PMID:36255050^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.