An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei

eLife

Hongjie Guo¹  Stephen Beverley¹  Angela Mehlert²  Jose Carlos Paredes Franco²  Michael AJ Ferguson²  Sebastian Damerow²  Giulia Bandini²  Maria Lucia Sempaio Guther² 

[1]Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United States

[2]Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom

关键词: kinetoplastid;    glycobiology;    mitochondria;    fucosyltranferase;    Trypanosoma;    Other;   

DOI  :  10.7554/eLife.70272

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in Trypanosoma brucei. Here we show that the single identifiable T. brucei fucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosyltransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif. Conditional null mutants of TbFUT1 demonstrated that it is essential for both the mammalian-infective bloodstream form and the insect vector-dwelling procyclic form. Unexpectedly, TbFUT1 was localized in the mitochondrion of T. brucei and found to be required for mitochondrial function in bloodstream form trypanosomes. Finally, the TbFUT1 gene was able to complement a Leishmania major mutant lacking the homologous fucosyltransferase gene (Guo et al., 2021). Together these results suggest that kinetoplastids possess an unusual, conserved and essential mitochondrial fucosyltransferase activity that may have therapeutic potential across trypanosomatids.

【 授权许可】

CC BY