Browsing by Author "Wallqvist, Anders"

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    The N-terminal domain of RfaH plays an active role in protein fold-switching
    (2021) Galaz-Davison, Pablo; Roman, Ernesto A.; Ramirez-Sarmiento, Cesar A.; Wallqvist, Anders; Elofsson, Arne; Wallqvist, Anders; Elofsson, Arne; Wallqvist, Anders; Elofsson, Arne; Wallqvist, Anders; Elofsson, Arne
    Author summary Proteins commonly adopt a single three-dimensional structure that is required for biological function. Nevertheless, proteins are not isolated in the cell, and the presence of binding partners can give rise to alternate structural configurations. Metamorphic proteins represent an extreme case of the latter, by folding into at least two well-defined configurations that are both structurally and functionally different. For RfaH, a virulence factor in enterobacteria, two distinct folds are found: an autoinhibited state in which its two protein domains strongly interact, and an active state in which these domains dissociate due to a specific DNA signal on RNA polymerases. This activation is accompanied by the refolding of the C-terminal domain (CTD) from an alpha-helical structure to a beta-barrel. Our work employs computational simulations to explore the role of the N-terminal domain (NTD) in regulating the metamorphic behavior of RfaH, determining that this domain has a major part in orienting and binding to the CTD in its alpha-helical fold, and in stabilizing an intermediate state instead of the fully folded beta-barrel. These results suggest that the NTD not only participates in stabilizing the autoinhibited state, but also aids in fold-switching back to it after active RfaH is released from RNA polymerase.