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An extended active-site motif controls the reactivity of the thioredoxin fold.

ABSTRACT: Proteins belonging to the thioredoxin (Trx) superfamily are abundant in all organisms. They share the same structural features, arranged in a seemingly simple fold, but they perform a multitude of functions in oxidative protein folding and electron transfer pathways. We use the C-terminal domain of the unique transmembrane reductant conductor DsbD as a model for an in-depth analysis of the factors controlling the reactivity of the Trx fold. We employ NMR spectroscopy, x-ray crystallography, mutagenesis, in vivo functional experiments applied to DsbD, and a comparative sequence analysis of Trx-fold proteins to determine the effect of residues in the vicinity of the active site on the ionization of the key nucleophilic cysteine of the -CXXC- motif. We show that the function and reactivity of Trx-fold proteins depend critically on the electrostatic features imposed by an extended active-site motif.

SUBMITTER: Mavridou DA

PROVIDER: S-EPMC3961690 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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An extended active-site motif controls the reactivity of the thioredoxin fold.

Mavridou Despoina A I DA Saridakis Emmanuel E Kritsiligkou Paraskevi P Mozley Erin C EC Ferguson Stuart J SJ Redfield Christina C

The Journal of biological chemistry 20140127 12

Proteins belonging to the thioredoxin (Trx) superfamily are abundant in all organisms. They share the same structural features, arranged in a seemingly simple fold, but they perform a multitude of functions in oxidative protein folding and electron transfer pathways. We use the C-terminal domain of the unique transmembrane reductant conductor DsbD as a model for an in-depth analysis of the factors controlling the reactivity of the Trx fold. We employ NMR spectroscopy, x-ray crystallography, muta ...[more]

PMID: 24469455

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