article published yes Laura Troussicot author 3d9cac31-413c-11eb-9514-d1ec2a7fb7f30000-0001-8297-8886 Alicia Vallet author Mikael Molin author Björn M. Burmann author Paul Schanda author 7B541462-FAF6-11E9-A490-E8DFE56974250000-0002-9350-7606 PaSc department Disulfide bond formation is fundamentally important for protein structure and constitutes a key mechanism by which cells regulate the intracellular oxidation state. Peroxiredoxins (PRDXs) eliminate reactive oxygen species such as hydrogen peroxide through a catalytic cycle of Cys oxidation and reduction. Additionally, upon Cys oxidation PRDXs undergo extensive conformational rearrangements that may underlie their presently structurally poorly defined functions as molecular chaperones. Rearrangements include high molecular-weight oligomerization, the dynamics of which are, however, poorly understood, as is the impact of disulfide bond formation on these properties. Here we show that formation of disulfide bonds along the catalytic cycle induces extensive μs time scale dynamics, as monitored by magic-angle spinning NMR of the 216 kDa-large Tsa1 decameric assembly and solution-NMR of a designed dimeric mutant. We ascribe the conformational dynamics to structural frustration, resulting from conflicts between the disulfide-constrained reduction of mobility and the desire to fulfill other favorable contacts. https://research-explorer.ista.ac.at/download/13095/13098/2023_JACS_Troussicot.pdf application/pdfno American Chemical Society2023 eng 0002-7863 1520-5126 37140345 00098590740000110.1021/jacs.3c01200 1451910700–10711 https://research-explorer.ista.ac.at/record/12820 Troussicot L, Vallet A, Molin M, Burmann BM, Schanda P. Disulfide-bond-induced structural frustration and dynamic disorder in a peroxiredoxin from MAS NMR. <i>Journal of the American Chemical Society</i>. 2023;145(19):10700–10711. doi:<a href="https://doi.org/10.1021/jacs.3c01200">10.1021/jacs.3c01200</a> L. Troussicot, A. Vallet, M. Molin, B.M. Burmann, P. Schanda, Journal of the American Chemical Society 145 (2023) 10700–10711. L. Troussicot, A. Vallet, M. Molin, B. M. Burmann, and P. Schanda, “Disulfide-bond-induced structural frustration and dynamic disorder in a peroxiredoxin from MAS NMR,” <i>Journal of the American Chemical Society</i>, vol. 145, no. 19. American Chemical Society, pp. 10700–10711, 2023. Troussicot, Laura, Alicia Vallet, Mikael Molin, Björn M. Burmann, and Paul Schanda. “Disulfide-Bond-Induced Structural Frustration and Dynamic Disorder in a Peroxiredoxin from MAS NMR.” <i>Journal of the American Chemical Society</i>. American Chemical Society, 2023. <a href="https://doi.org/10.1021/jacs.3c01200">https://doi.org/10.1021/jacs.3c01200</a>. Troussicot L, Vallet A, Molin M, Burmann BM, Schanda P. 2023. Disulfide-bond-induced structural frustration and dynamic disorder in a peroxiredoxin from MAS NMR. Journal of the American Chemical Society. 145(19), 10700–10711. Troussicot, L., Vallet, A., Molin, M., Burmann, B. M., &#38; Schanda, P. (2023). Disulfide-bond-induced structural frustration and dynamic disorder in a peroxiredoxin from MAS NMR. <i>Journal of the American Chemical Society</i>. American Chemical Society. <a href="https://doi.org/10.1021/jacs.3c01200">https://doi.org/10.1021/jacs.3c01200</a> Troussicot, Laura, et al. “Disulfide-Bond-Induced Structural Frustration and Dynamic Disorder in a Peroxiredoxin from MAS NMR.” <i>Journal of the American Chemical Society</i>, vol. 145, no. 19, American Chemical Society, 2023, pp. 10700–10711, doi:<a href="https://doi.org/10.1021/jacs.3c01200">10.1021/jacs.3c01200</a>. 130952023-05-28T22:01:04Z2024-10-09T21:05:30Z