Etudes Biochimique et Structurale de DsbA1, DsbA2 et DsbA3 : les trois homologues à l'oxydoréductase de Thiol-disulfure DsbA chez Neisseria meningitidis.

Abstract : Neisseria meningitidis is an invasive bacterial pathogen causing life-threatening infection. Host-pathogen interactions depend on the correct folding of many surface-exposed proteins, which often requires disulfide bond formation. In Gram-negative bacteria, the synthesis of disulfide bonds is catalyzed by the thiol-disulfide oxidoreductase DsbA. N. meningitidis possesses three genes encoding three active DsbA (DsbA1, DsbA2 and DsbA3). DsbA1 and DsbA2 are lipoproteins involved in the virulence while DsbA3 is a soluble periplasmic protein non related to the virulence. This work reports the biochemical characterisation of the three neisserial enzymes and the crystal structures of DsbA1 and DsbA3. DsbA1 and DsbA3 adopt the classical Escherichia coli DsbA fold. The most striking feature shared by all three proteins is their exceptional oxidizing power. With a redox potential of -80 mV, they are the most oxidizing thioredoxin-like enzymes known to date. For each of these enzymes, the threonine residue found within the active site region plays a key role in dictating this extraordinary oxidizing power. Consistent with these findings, thermal studies indicate that their reduced form is also extremely stable. This result highlights how residues located outside the CXXC motif may influence the redox potential of members of the thioredoxin family. In addition, this functional and structural study shows that the phenotype associated with DsbA3 in N. meningitidis cannot be explained by a difference of redox activity.
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Submitted on : Monday, December 14, 2009 - 9:21:46 AM
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Céline Lafaye. Etudes Biochimique et Structurale de DsbA1, DsbA2 et DsbA3 : les trois homologues à l'oxydoréductase de Thiol-disulfure DsbA chez Neisseria meningitidis.. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00440935⟩

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