TY - JOUR
T1 - An essential, kinetoplastid-specific GDP-FUC
T2 - P-d-gal a-1,2- fucosyltransferase is located in the mitochondrion of trypanosoma brucei
AU - Bandini, Giulia
AU - Damerow, Sebastian
AU - Guther, Maria Lucia Sampaio
AU - Guo, Hongjie
AU - Mehlert, Angela
AU - Franco, Jose Carlos Paredes
AU - Beverley, Stephen M.
AU - Ferguson, Michael A.J.
N1 - Publisher Copyright:
© 2021, eLife Sciences Publications Ltd. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - 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: P-D- galactose a-1,2-fucosyltransferase with an apparent preference for a Gaipi,3GlcNAcpi-O-R acceptor motif. Conditional null mutants of TbFUTl 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 TbFUTl 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.
AB - 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: P-D- galactose a-1,2-fucosyltransferase with an apparent preference for a Gaipi,3GlcNAcpi-O-R acceptor motif. Conditional null mutants of TbFUTl 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 TbFUTl 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.
UR - http://www.scopus.com/inward/record.url?scp=85114407915&partnerID=8YFLogxK
U2 - 10.7554/eLife.70272
DO - 10.7554/eLife.70272
M3 - Article
C2 - 34410224
AN - SCOPUS:85114407915
SN - 2050-084X
VL - 10
JO - eLife
JF - eLife
ER -