Journal
BIOMOLECULES
Volume 10, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/biom10091250
Keywords
click chemistry; EGF-LD; O-fucosylation; phylogeny; Pofut1; Wif1
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Funding
- French Ministry of Higher Education and Research doctoral fellowship
- GlyCanColor project within the CORC (Comite d'Orientation de la Recherche sur le Cancer en Limousin, 2016) program
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The Wnt Inhibitory Factor 1 (Wif1), known to inhibit Wnt signaling pathways, is composed of a WIF domain and five EGF-like domains (EGF-LDs) involved in protein interactions. Despite the presence of a potentialO-fucosylation site in its EGF-LDs III and V, theO-fucose sites occupancy has never been demonstrated for WIF1. In this study, a phylogenetic analysis on the distribution, conservation and evolution of Wif1 proteins was performed, as well as biochemical approaches focusing onO-fucosylation sites occupancy of recombinant mouse WIF1. In the monophyletic group of gnathostomes, we showed that the consensus sequence forO-fucose modification by Pofut1 is highly conserved in Wif1 EGF-LD III while it was more divergent in EGF-LD V. Using click chemistry and mass spectrometry, we demonstrated that mouse WIF1 was only modified with a non-extendedO-fucose on its EGF-LD III. In addition, a decreased amount of mouse WIF1 in the secretome of CHO cells was observed when theO-fucosylation site in EGF-LD III was mutated. Based on sequence comparison and automated protein modeling, we suggest that the absence ofO-fucose on EGF-LD V of WIF1 in mouse and probably in most gnathostomes, could be related to EGF-LD V inability to interact with POFUT1.
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