The membrane-bound flavocytochrome MsrQ is a substrate of the cytosolic flavin reductase Fre in Escherichia coli - Archive ouverte HAL Access content directly
Journal Articles ACS Chemical Biology Year : 2021

The membrane-bound flavocytochrome MsrQ is a substrate of the cytosolic flavin reductase Fre in Escherichia coli

Abstract

MsrPQ is a new type of methionine sulfoxide reductase (Msr) system found in bacteria. It is specifically involved in the repair of periplasmic methionine residues that are oxidized by hypochlorous acid. MsrP is a periplasmic molybdo-enzyme that carries out the Msr activity by itself, whereas MsrQ, an integral membrane bound hemoprotein, acts as the physiological partner of MsrP to provide electrons for catalysis. Although MsrQ, previously called YedZ, has been associated since long to a protein superfamily named FRD (ferric reductase domain), including the eukaryotic NADPH oxidases and STEAP proteins, its biochemical properties are still sparsely documented. In this work, we have investigated the cofactors content of the E.coli MsrQ and its mechanism of reduction by the cytosolic flavin reductase Fre. We showed by EPR spectroscopy that MsrQ contains a single HALS (highly-anisotropic low-spin) b-type heme, located on the periplasmic side of the membrane. We further demonstrated that MsrQ holds a FMN cofactor that occupies the site where a second heme binds in other members of the FDR superfamily, on the cytosolic side of the membrane. EPR spectroscopy indicates that the FMN cofactor can accommodate a radical semiquinone form. The cytosolic flavin reductase Fre was previously shown to reduce the MsrQ heme. Here, we demonstrated that Fre uses the FMN MsrQ cofactor as a substrate to catalyze the electron transfer from cytosolic NADH to the heme. Formation of a specific complex between MsrQ and Fre could favor this unprecedented mechanism, which most likely involves a transfer of the reduced FMN cofactor from the Fre active site to MsrQ.
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Dates and versions

hal-03320876 , version 1 (16-08-2021)

Identifiers

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Christelle Caux, Bruno Guigliarelli, Corinne Vivès, Frédéric Biaso, Marius Horeau, et al.. The membrane-bound flavocytochrome MsrQ is a substrate of the cytosolic flavin reductase Fre in Escherichia coli. ACS Chemical Biology, 2021, 16 (11), pp.2547-2559. ⟨10.1021/acschembio.1c00613⟩. ⟨hal-03320876⟩
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