Unveiling the activation dynamics of a fold-switch bacterial glycosyltransferase by 19F NMR.
Unveiling the activation dynamics of a fold-switch bacterial glycosyltransferase by 19F NMR.
J Biol Chem. 2020 May 20;:
Authors: Liebau J, Tersa M, Trastoy B, Patrick J, Rodrigo-Unzueta A, Corzana F, Sparrman T, Guerin ME, Mäler L
Abstract
Fold-switch pathways remodel the secondary structure topology of proteins in response to the cellular environment. It is a major challenge to understand the dynamics of these folding processes. Here we conducted an in-depth analysis of the ?-helix-to-?-strand and ?-strand-to-?-helix transitions and domain motions displayed by the essential mannosyltransferase PimA from mycobacteria. Using 19F NMR, we identified four functionally relevant states of PimA that co-exist in dynamic equilibria on millisecond-to-second timescales in solution. We discovered that fold-switching is a slow process, on the order of seconds, whereas domain motions occur simultaneously but are substantially faster, on the order of milliseconds. Strikingly, the addition of substrate accelerated the fold-switching dynamics of PimA. We propose a model in which the fold-switching dynamics constitute a mechanism for PimA activation.
PMID: 32434931 [PubMed - as supplied by publisher]
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