| Structural highlights
Function
[GPX41_MOUSE] Protects cells against membrane lipid peroxidation and cell death (PubMed:12566075). Required for normal sperm development and male fertility (PubMed:19417079). Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development (PubMed:12566075). Protects from radiation and oxidative damage (PubMed:12566075). Essential for maturation and survival of photoreceptor cells (PubMed:22207760). Plays a role in a primary T cell response to viral and parasitic infection by protecting T cells from ferroptosis, a cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species, and by supporting T cell expansion (PubMed:25824823).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The mammalian glutathione peroxidase (GPx) family is a key component of the cellular antioxidative defence system. Within this family, GPx4 has unique features as it accepts a large class of hydroperoxy lipid substrates and has a plethora of biological functions, including sperm maturation, regulation of apoptosis and cerebral embryogenesis. In this paper, the structure of the cytoplasmic isoform of mouse phospholipid hydroperoxide glutathione peroxidase (O70325-2 GPx4) with selenocysteine 46 mutated to cysteine is reported solved at 1.8 A resolution using X-ray crystallography. Furthermore, solution data of an isotope-labelled GPx protein are presented.
Crystal and solution structural studies of mouse phospholipid hydroperoxide glutathione peroxidase 4.,Janowski R, Scanu S, Niessing D, Madl T Acta Crystallogr F Struct Biol Commun. 2016 Oct 1;72(Pt 10):743-749. Epub 2016, Sep 22. PMID:27710939[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yant LJ, Ran Q, Rao L, Van Remmen H, Shibatani T, Belter JG, Motta L, Richardson A, Prolla TA. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic Biol Med. 2003 Feb 15;34(4):496-502. PMID:12566075
- ↑ Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E, Radmark O, Wurst W, Bornkamm GW, Schweizer U, Conrad M. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab. 2008 Sep;8(3):237-48. PMID:18762024 doi:http://dx.doi.org/S1550-4131(08)00212-X
- ↑ Schneider M, Forster H, Boersma A, Seiler A, Wehnes H, Sinowatz F, Neumuller C, Deutsch MJ, Walch A, Hrabe de Angelis M, Wurst W, Ursini F, Roveri A, Maleszewski M, Maiorino M, Conrad M. Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J. 2009 Sep;23(9):3233-42. doi: 10.1096/fj.09-132795. Epub 2009 May 5. PMID:19417079 doi:http://dx.doi.org/10.1096/fj.09-132795
- ↑ Ueta T, Inoue T, Furukawa T, Tamaki Y, Nakagawa Y, Imai H, Yanagi Y. Glutathione peroxidase 4 is required for maturation of photoreceptor cells. J Biol Chem. 2012 Mar 2;287(10):7675-82. doi: 10.1074/jbc.M111.335174. Epub 2011 , Dec 29. PMID:22207760 doi:http://dx.doi.org/10.1074/jbc.M111.335174
- ↑ Matsushita M, Freigang S, Schneider C, Conrad M, Bornkamm GW, Kopf M. T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J Exp Med. 2015 Apr 6;212(4):555-68. doi: 10.1084/jem.20140857. Epub 2015 Mar 30. PMID:25824823 doi:http://dx.doi.org/10.1084/jem.20140857
- ↑ Janowski R, Scanu S, Niessing D, Madl T. Crystal and solution structural studies of mouse phospholipid hydroperoxide glutathione peroxidase 4. Acta Crystallogr F Struct Biol Commun. 2016 Oct 1;72(Pt 10):743-749. Epub 2016, Sep 22. PMID:27710939 doi:http://dx.doi.org/10.1107/S2053230X16013686
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