Recognition of Complex Core-Fucosylated N-Glycans by a Mini Lectin

Aurore Cabanettes (1) , Lukas Perkams (2) , Carolina Spies , Carlo Unverzagt , Annabelle Varrot (1)

1 CERMAV - Centre de Recherches sur les Macromolécules Végétales
2 Bioorganische Chemie, Universität Bayreuth

We recombinantly produced and characterized the mini fungal lectin PhoSL. Despite a length of only 40 amino acids, PhoSL exclusively recognizes N-glycans with α1,6-linked fucose. Core fucosylation influences the intrinsic properties and bioactivities of mammalian N-glycoproteins and its level is linked to various cancers. Thus, PhoSL serves as a promising tool for glycoprofiling. Without structural precedence, we solved its crystal structure using the zinc anomalous signal. We revealed an interlaced trimer creating a novel protein fold termed β-prism III. Three biantennary core fucosylated N-glycan azides of 8 to 12 sugars were cocrystallized with PhoSL. The resulting highly resolved structures gave a detailed view on how the exclusive recognition of α1,6-fucosylated N-glycans by such a small protein occurs. This work also provided a protein consensus motif for the observed specificity as well as a glimpse on N-glycan flexibility upon binding.

Mots clés: recombinant lectin; core fucosylation; β-prism fold; structural biology; glycosylation

Domaines: Cristallographie; Biochimie, Biologie Moléculaire

Aurore Cabanettes, Lukas Perkams, Carolina Spies, Carlo Unverzagt, Annabelle Varrot. Recognition of Complex Core-Fucosylated N-Glycans by a Mini Lectin. Angewandte Chemie International Edition, 2018, 57 (32), pp.10178 - 10181. ⟨10.1002/anie.201805165⟩. ⟨hal-01880792⟩