Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 Å resolution

Declercq, Jean‐Paul; Evrard, C.; Clippe, André; Stricht, Delphine Vander; Bernard, Alfred; Knoops, Bernard

doi:10.1006/jmbi.2001.4853

Cited by 246 publications

(235 citation statements)

References 26 publications

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“…Similar large scale conformational editing through redox switching has been observed in the E. coli H 2 O 2 transcription factor, OxyR (22). Furthermore, reconciliation of biochemical evidence and the location of catalytic cysteine residues in the thioredoxin-like structure of peroxiredoxin 5 necessitate a conformational change during peroxide reduction (23). The rearrangement of the ␤-sheet observed for CLIC1 may, therefore, not be a unique feature of the CLIC protein family but, rather, a structural duality capable of being tolerated by the thioredoxin fold of some proteins.…”

Section: Discussionmentioning

confidence: 55%

The Intracellular Chloride Ion Channel Protein CLIC1 Undergoes a Redox-controlled Structural Transition

Littler

Harrop

Fairlie

et al. 2004

Journal of Biological Chemistry

197

355

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Most proteins adopt a well defined three-dimensional structure; however, it is increasingly recognized that some proteins can exist with at least two stable conformations. Recently, a class of intracellular chloride ion channel proteins (CLICs) has been shown to exist in both soluble and integral membrane forms. The structure of the soluble form of CLIC1 is typical of a soluble glutathione S-transferase superfamily protein but contains a glutaredoxin-like active site. In this study we show that on oxidation CLIC1 undergoes a reversible transition from a monomeric to a non-covalent dimeric state due to the formation of an intramolecular disulfide bond (Cys-24 -Cys-59). We have determined the crystal structure of this oxidized state and show that a major structural transition has occurred, exposing a large hydrophobic surface, which forms the dimer interface. The oxidized CLIC1 dimer maintains its ability to form chloride ion channels in artificial bilayers and vesicles, whereas a reducing environment prevents the formation of ion channels by CLIC1. Mutational studies show that both Cys-24 and Cys-59 are required for channel activity.Chloride ion channels control a variety of cellular processes that are central to normal function and disease states (1). The CLIC 1 family is a recently identified class of Cl Ϫ channel proteins that consists of seven members (p64, parchorin, CLIC1-5) (2, 3). A conserved C-terminal CLIC module of ϳ240 amino acids is present in each member of the family with several members containing additional, unrelated Nterminal domains. Most CLICs are localized to intracellular membranes and have been linked to functions including apoptosis, pH, and cell cycle regulation (4 -6). The CLIC ion channels are unusual in that they possess both soluble and integral membrane forms (2). In this regard they are similar to some bacterial toxins and several classes of intracellular proteins including Bcl-x L and the annexins (7). Our understanding of how such dual natured proteins enter the membrane is limited by the dearth of high resolution structures for key states in this process.We have recently determined the crystal structure of a soluble monomeric form of CLIC1 (8) and found that it is a structural homologue of the GST superfamily of proteins (9). This soluble form of CLIC1 consists of two domains, the N-domain possessing a thioredoxin fold closely resembling glutaredoxin and an all ␣-helical C-domain, which is typical of the GST superfamily. CLIC1 contains an intact glutathione-binding site that was shown to covalently bind glutathione via a conserved CLIC cysteine residue, Cys-24. This led to the suggestion that CLIC1 function may be under redox control, possibly via reactive oxygen or nitrogen species.The structure and stoichiometry of the integral membrane form of the CLIC proteins is still unclear. Electrophysiology of purified, soluble (Escherichia coli-expressed) recombinant CLIC1 in reconstituted artificial bilayers shows that CLIC1 alone is sufficient for chloride ion channel formation (8, 1...

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Section: Discussionmentioning

confidence: 55%

The Intracellular Chloride Ion Channel Protein CLIC1 Undergoes a Redox-controlled Structural Transition

Littler

Harrop

Fairlie

et al. 2004

Journal of Biological Chemistry

197

355

View full text Add to dashboard Cite

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“…NIH-PA Author Manuscript NIH-PA Author Manuscript superfamily [7,8]. Unlike most peroxidases-which contain a heme ring at their active site (e.g., cytochrome c peroxidase) or a redox-sensitive moiety like selenocysteine (glutathione peroxidase; GPx), vanadium (algal bromoperoxide), or flavin (bacterial NADH peroxidase)-Prxs lack cofactor metal ions, prosthetic groups, or cofactors [9].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

Peterson

Luckhart

2006

Free Radical Biology and Medicine

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Malaria parasite infection in anopheline mosquitoes induces nitrosative and oxidative stresses that limit parasite development, but also damage mosquito tissues in proximity to the response. Based on these observations, we proposed that cellular defenses in the mosquito may be induced to minimize self-damage. Specifically, we hypothesized that peroxiredoxins (Prxs), enzymes known to detoxify reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), protect mosquito cells. We identified an Anopheles stephensi 2-Cys Prx ortholog of Drosophila melanogaster Prx-4783, which protects fly cells against oxidative stresses. To assess function, AsPrx-4783 was overexpressed in D. melanogaster (S2) and in A. stephensi (MSQ43) cells and silenced in MSQ43 cells with RNA interference before treatment with various ROS and RNOS. Our data revealed that AsPrx-4783 and DmPrx-4783 differ in host cell protection and that AsPrx-4783 protects A. stephensi cells against stresses that are relevant to malaria parasite infection in vivo, namely nitric oxide (NO), hydrogen peroxide, nitroxyl, and peroxynitrite. Further, AsPrx-4783 expression is induced in the mosquito midgut by parasite infection at times associated with peak nitrosative and oxidative stresses. Hence, whereas the NO-mediated defense response is toxic to both host and parasite, AsPrx-4783 may shift the balance in favor of the mosquito. KeywordsMalaria; Mosquito; Peroxiredoxin; Plasmodium; Anopheles; Nitric oxide; Nitrosative stress; Free radicals It has long been recognized that reactive oxygen species (ROS) and, more recently, reactive nitrogen oxide species (RNOS) function to defend hosts against pathogens [1]. Although ROS and RNOS are cytotoxic to pathogens and parasites, they also induce oxidative and nitrosative stresses in the host and can damage host tissues [1]. Host protection against oxidative and nitrosative stress, therefore, is vital for homeostasis and hence survival. Gene products that confer protection against ROS are well known. In contrast, gene products that confer protection against RNOS have been identified, but are less well studied. The peroxiredoxins (Prxs) are a recently discovered family of antioxidant peroxidases that can reduce hydrogen peroxide and alkyl hydroperoxides to water and the corresponding alcohols, respectively, and can protect cells from widely divergent organisms against a variety of nitrosative stress challenges [2][3][4][5][6].Prxs do not show sequence homology to other known antioxidant enzymes. Crystal structures of PrxI, II, V, and VI have revealed that Prxs are novel members of the thioredoxin fold * Corresponding author. Fax: +1 530 752 8692. E-mail address: sluckhart@ucdavis.edu (S. Luckhart). NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript superfamily [7,8]. Unlike most peroxidases-which contain a heme ring at their active site (e.g., cytochrome c peroxidase) or a redox-sensitive moiety like selenocysteine (glutathione peroxidase; GPx), vanadium (algal bro...

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“…Crystal structure analysis groups Prxs into the thioredoxin superfamily (8). Type II Prxs (PRDX5) act as monomers (8).…”

mentioning

confidence: 99%

“…Type II Prxs (PRDX5) act as monomers (8). 1-Cys Prxs (HORF6) are monomeric too but form homodimers at protein concentrations of Ͼ1 mg/ml (9).…”

mentioning

confidence: 99%

Reaction Mechanism of Plant 2-Cys Peroxiredoxin

König¹,

Lotte

Plessow

et al. 2003

Journal of Biological Chemistry

170

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Barley 2-cysteine peroxiredoxin (2-Cys Prx) was analyzed for peroxide reduction, quaternary structure, thylakoid attachment, and function as well as in vivo occurrence of the inactivated form, with emphasis on the role of specific amino acid residues. Data presented show the following. 1) 2-Cys Prx has a broad substrate specificity and reduces even complex lipid peroxides such as phosphatidylcholine dilineoyl hydroperoxide, although at low rates. 2) 2-Cys Prx partly becomes irreversibly oxidized by peroxide substrates during the catalytic cycle in a concentration-dependent manner, particularly by bulky hydroperoxides.

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Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 Å resolution

Cited by 246 publications

References 26 publications

The Intracellular Chloride Ion Channel Protein CLIC1 Undergoes a Redox-controlled Structural Transition

The Intracellular Chloride Ion Channel Protein CLIC1 Undergoes a Redox-controlled Structural Transition

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

Reaction Mechanism of Plant 2-Cys Peroxiredoxin

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