Disulfide-Bond-Induced Structural Frustration and Dynamic Disorder in a Peroxiredoxin from MAS NMR
Artikel i vetenskaplig tidskrift, 2023

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.

Författare

Laura Troussicot

Institute of Science and Technology Austria

Göteborgs universitet

Université Grenoble Alpes

Alicia Vallet

Université Grenoble Alpes

Mikael Molin

Göteborgs universitet

Chalmers, Life sciences, Systembiologi

Björn M. Burmann

Göteborgs universitet

Paul Schanda

Institute of Science and Technology Austria

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 145 19 10700-10711

Ämneskategorier

Biokemi och molekylärbiologi

DOI

10.1021/jacs.3c01200

PubMed

37140345

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Senast uppdaterat

2024-03-07