线粒体铁蛋白
位於5號人類染色體的基因
线粒体铁蛋白是一种存在于线粒体内的亚铁氧化酶。这种氧化还原酶与细胞质基质中的铁蛋白在结构与功能上高度同源,两者理化性质和结构极为相似,都具有铁摄取、结合和储存功能。人类的线粒体铁蛋白由FTMT基因编码。[2]
线粒体铁蛋白 | |
---|---|
![]() | |
线粒体铁蛋白的晶体结构[1] | |
识别 | |
符号 | MtF |
Entrez | 94033 |
HUGO | 17345 |
OMIM | 608847 |
RefSeq | NM_177478 |
UniProt | Q8N4E7 |
其他资料 | |
EC编号 | 1.16.3.1 |
基因座 | 5 q23.1 |
结构
编辑人类线粒体铁蛋白的前体蛋白由242个氨基酸残基组成(其N端含有长度为57aa的引导链,用于将其带入线粒体),相对分子质量约为30kDa,氨基酸序列与铁蛋白重链和铁蛋白轻链的同源性分别为79%和63%。成熟线粒体铁蛋白蛋白由185个氨基酸残基组成(一说由182个氨基酸残基),相对分子质量约为22kDa。这些亚基可以相互结合形成一个拥有亚铁氧化酶活性的蛋白质壳层,用于隔离有害的游离亚铁离子。[3]尽管铁蛋白的重链和线粒体铁蛋白在晶体结构上极为相似,但前者是由重链和轻链组成的24-杂多聚体(heteropolymer),而后者是由24个相同亚基组成的纯多聚体(homopolymer)。[4]线粒体铁蛋白有67%是螺旋形的,拉氏构象图显示线粒体铁蛋白大部分皆为α螺旋,只拥有少量β折叠结构。
作用
编辑线粒体铁蛋白能在调节线粒体内的铁稳态、保护线粒体免受氧化应激损伤,以及调节血红素和铁硫基团生物合成等方面发挥着重要作用。[5]在铁粒幼红细胞性贫血患者的幼红细胞的血红素合成酶有缺陷,为防止亚铁离子不能参与血红素合成而大量蓄积在线粒体内导致铁负荷升高,线粒体铁蛋白表达水平显著上调,将过多的亚铁离子氧化为高铁离子储存在线粒体铁蛋白的壳状结构中。环形铁粒幼红细胞是上述贫血类型的特异性标志物,其核周线粒体内的多数铁都以线粒体铁蛋白的形式沉积。[6]在铁粒幼红细胞性贫血的病理状况下,线粒体铁蛋白高表达的幼红细胞线粒体并无功能、寿命异常,说明线粒体铁蛋白具有保护线粒体的重要作用。
参考文献
编辑- ^ PDB 1r03
- ^ Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, Sanford D, Arosio P, Drysdale J. A human mitochondrial ferritin encoded by an intronless gene (PDF). Journal of Biological Chemistry. July 6, 2001, 276 (27): 24437–24440 [2011-09-05]. PMID 11323407. doi:10.1074/jbc.C100141200. (原始内容 (PDF)存档于2018-07-24) (英语).
- ^ Drysdale J, Arosio P, Invernizzi R, Cazzola M, Volz A, Corsi B, Biasiotto G, Levi S. Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol. Dis. Nov–Dec 2002, 29 (3): 376–383. PMID 12547228. doi:10.1006/bcmd.2002.0577 (英语).
- ^ 孙蕾、袁粒星、高举. 线粒体铁蛋白分子生物学及其与机体铁代谢的关系. International Journal of Blood Transfusion and Hematology. 2007, 30 (5): 447–449 (中文).
- ^ Langlois d'Estaintot B, Santambrogio P, Granier T, Gallois B, Chevalier JM, Précigoux G, Levi S, Arosio P. Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. Journal of Biological Chemistry. Jul 2, 2004, 340 (2): 277–293 [2011-09-05]. PMID 15201052. doi:10.1016/j.jmb.2004.04.036. (原始内容存档于2016-04-07) (英语).
- ^ Cazzola M, Invernizzi R, Bergamaschi G, Levi S, Corsi B, Travaglino E, Rolandi V, Biasiotto G, Drysdale J, Arosio P. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood. Mar 1, 2003, 101 (5): 1996–2000 [2011-09-06]. PMID 12406866. doi:10.1182/blood-2002-07-2006. (原始内容存档于2019-11-02) (英语).
扩展阅读
编辑- Zanella I, Derosas M, Corrado M; et al. The effects of frataxin silencing in HeLa cells are rescued by the expression of human mitochondrial ferritin.. Biochim. Biophys. Acta. 2008, 1782 (2): 90–8. PMID 18160053. doi:10.1016/j.bbadis.2007.11.006.
- Wilkinson J, Di X, Schönig K; et al. Tissue-specific expression of ferritin H regulates cellular iron homoeostasis in vivo.. Biochem. J. 2006, 395 (3): 501–7. PMC 1462685 . PMID 16448386. doi:10.1042/BJ20060063.
- Iwasaki K, Mackenzie EL, Hailemariam K; et al. Hemin-mediated regulation of an antioxidant-responsive element of the human ferritin H gene and role of Ref-1 during erythroid differentiation of K562 cells.. Mol. Cell. Biol. 2006, 26 (7): 2845–56. PMC 1430308 . PMID 16537925. doi:10.1128/MCB.26.7.2845-2856.2006.
- Hasan MR, Tosha T, Theil EC. Ferritin contains less iron (59Fe) in cells when the protein pores are unfolded by mutation.. J. Biol. Chem. 2008, 283 (46): 31394–400. PMC 2581568 . PMID 18805796. doi:10.1074/jbc.M806025200.
- Faniello MC, Fregola A, Nisticò A; et al. Detection and functional analysis of an SNP in the promoter of the human ferritin H gene that modulates the gene expression.. Gene. 2006, 377: 1–5. PMID 16797877. doi:10.1016/j.gene.2006.02.034.
- Iwasaki K, Hailemariam K, Tsuji Y. PIAS3 interacts with ATF1 and regulates the human ferritin H gene through an antioxidant-responsive element.. J. Biol. Chem. 2007, 282 (31): 22335–43. PMC 2409283 . PMID 17565989. doi:10.1074/jbc.M701477200.
- MacKenzie EL, Tsuji Y. Elevated intracellular calcium increases ferritin H expression through an NFAT-independent post-transcriptional mechanism involving mRNA stabilization.. Biochem. J. 2008, 411 (1): 107–13. PMC 2702759 . PMID 18076382. doi:10.1042/BJ20071544.
- Fisher J, Devraj K, Ingram J; et al. Ferritin: a novel mechanism for delivery of iron to the brain and other organs.. Am. J. Physiol., Cell Physiol. 2007, 293 (2): C641–9. PMID 17459943. doi:10.1152/ajpcell.00599.2006.
- Campanella A, Rovelli E, Santambrogio P; et al. Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia.. Hum. Mol. Genet. 2009, 18 (1): 1–11. PMID 18815198. doi:10.1093/hmg/ddn308.
- Bou-Abdallah F, Biasiotto G, Arosio P, Chasteen ND. The putative "nucleation site" in human H-chain ferritin is not required for mineralization of the iron core.. Biochemistry. 2004, 43 (14): 4332–7. PMID 15065877. doi:10.1021/bi0498813.
- Binning RC, Bacelo DE. Computational modeling of the dizinc-ferroxidase complex of human H ferritin: direct comparison of the density functional theory calculated and experimental structures.. J. Biol. Inorg. Chem. 2009, 14 (8): 1199–208. PMID 19585161. doi:10.1007/s00775-009-0563-z.
- MacKenzie EL, Ray PD, Tsuji Y. Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress.. Free Radic. Biol. Med. 2008, 44 (9): 1762–71. PMC 2682214 . PMID 18325346. doi:10.1016/j.freeradbiomed.2008.01.031.
- Bou-Abdallah F, Santambrogio P, Levi S; et al. Unique iron binding and oxidation properties of human mitochondrial ferritin: a comparative analysis with Human H-chain ferritin.. J. Mol. Biol. 2005, 347 (3): 543–54. PMID 15755449. doi:10.1016/j.jmb.2005.01.007.
- Faniello MC, Di Sanzo M, Quaresima B; et al. p53-mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y.. Int. J. Biochem. Cell Biol. 2008, 40 (10): 2110–9. PMID 18372207. doi:10.1016/j.biocel.2008.02.010.
- Snyder AM, Wang X, Patton SM; et al. Mitochondrial ferritin in the substantia nigra in restless legs syndrome.. J. Neuropathol. Exp. Neurol. 2009, 68 (11): 1193–9. PMC 3024883 . PMID 19816198. doi:10.1097/NEN.0b013e3181bdc44f.