9VBZ

Lectin FRIL from Lablab purpureus complexed to oligomannose

Summary for 9VBZ

• Entry DOI: 10.2210/pdb9vbz/pdb
• Related: 9VBW 9VBX 9VBY 9VC0
• EMDB information: 64937
• Descriptor: Flt3 receptor-interacting lectin, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: flt3 receptor-interacting lectin, carbohydrate binding protein, lectin, glycoprotein, high-mannose type glycan. oms-fril, fril, plant protein
• Biological source: Lablab purpureus
• Total number of polymer chains: 4
• Total formula weight: 116979.50

Authors

Nguyen, V.H.T.,Liu, Y.M.,Ma, C. (deposition date: 2025-06-05, release date: 2026-03-18, Last modification date: 2026-03-25)

Primary citation

Liu, Y.M.,Nguyen, H.T.V.,Chen, X.,Shahed-Al-Mahmud, M.,Chen, T.H.,Liao, K.S.,Lo, J.M.,Kan, T.C.,Ren, C.T.,Ma, C.
Altering the carbohydrate-binding specificity of the legume lectin FRIL through structure-guided engineering.
Nat Commun, 2026

PubMed Abstract: FRIL is a legume lectin from the hyacinth bean that has broad-spectrum antiviral activity. A distinctive trait of FRIL among similar mannose/glucose-specific legume lectins is that FRIL shows specificity for complex type N-glycans. We postulate that an extended binding site on FRIL facilitates this ligand selectivity. Here, we show legume lectin carbohydrate recognition domain (CRD) loop B is the main determinant of complex versus high-mannose N-glycan specificity in FRIL and Concanavalin A (ConA), respectively. First, we find that the inactive precursors of recombinant FRIL (rFRIL) and proConA (rproConA) can be activated via deglycosylation. Secondly, the cryo-EM structures of inactive apo rFRIL, active FRIL in complex with Galβ1,4-(Fucα1,3-)GlcNAcβ1,2-Man tetrasaccharide, and active rFRIL in complex with MannoseGlcNAc (Man9) N-glycan are determined, and residues H102 and Y101 on loop B are identified as crucial for complex glycan recognition. Finally, we swapped loop B residues 101 and 102 alongside loop C residue 145 on FRIL to their structural equivalent on ConA, resulting in a FRIL mutant that binds exclusively to high mannose N-glycans. Taken together, we have established a process of activating recombinant FRIL and related lectins through deglycosylation, and demonstrated the crucial role that loop B residues play in establishing oligosaccharide specificity.

PubMed: 41786775
DOI: 10.1038/s41467-026-70188-7

Experimental method

ELECTRON MICROSCOPY (2.56 Å)