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1دورية أكاديمية
المؤلفون: Bexkens, M.L. (Michiel), Zimorski, V. (Verena), Sarink, M.J. (Maarten J.), Wienk, H. (Hans), Brouwers, J.F. (Jos), Jonckheere, J.F. (Johan) de, Martin, W. (William), Opperdoes, F.R. (Fred), Hellemond, J.J. (Jaap) van, Tielens, A.G.M. (Lodewijk)
المصدر: Cell Reports
مصطلحات موضوعية: aerobic energy metabolism, alternative oxidase, electron-transport chain, fatty acid oxidation, Naegleria, PAM
الوصف: Naegleria gruberi is a free-living non-pathogenic amoeboflagellate and relative of Naegleria fowleri, a deadly pathogen causing primary amoebic meningoencephalitis (PAM). A genomic analysis of N. gruberi exists, but physiological evidence for its core energy metabolism or in vivo growth substrates is lacking. Here, we show that N. gruberi trophozoites need oxygen for normal functioning and growth and that they shun both glucose and amino acids as growth substrates. Trophozoite growth depends mainly upon lipid oxidation via a mitochondrial branched respiratory chain, both ends of which require oxygen as final electron acceptor. Growing N. gruberi trophozoites thus have a strictly aerobic energy metabolism with a marked substrate preference for the oxidation of fatty acids. Analyses of N. fowleri genome data and comparison with those of N. gruberi indicate that N. fowleri has the same type of metabolism. Specialization to oxygen-dependent lipid breakdown represents an additional metabolic strategy in protists. Bexkens et al. show that N. gruberi amoebae live preferably on lipids, for which they need oxygen, a lifestyle largely unknown among protists. This challenges existing views about its energy metabolism, with implications for treatment of its pathogenic relative, N. fowleri, the brain-eating agent of primary amoebic men
وصف الملف: application/pdf
العلاقة: http://repub.eur.nl/pub/111145Test; urn:hdl:1765/111145
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2دورية أكاديمية
المؤلفون: Faridounnia, M. (Maryam), Wienk, H. (Hans), Kovačič, L. (Lidija), Folkers, G.E. (Gert), Jaspers, N.G.J. (Nicolaas), Kaptein, R. (Robert), Hoeijmakers, J.H.J. (Jan), Boelens, R. (Rolf)
المصدر: Journal of Biological Chemistry vol. 290 no. 33, pp. 20541-20555
الوصف: The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe 231 , Leu 231 lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation.
العلاقة: http://repub.eur.nl/pub/86801Test; urn:hdl:1765/86801
