Fig. 3: Classical GT-B fold and structural conservation and diversification of clade 1 FUTs.

a Superposition of the catalytic domains from human FUT8 (PDB: 6TKV), FUT9 (PDB: 8D0Q), POFUT1 (PDB: 5UXH), and POFUT2 (PDB: 4AP6) reveals a conserved GT-B fold shared by all structurally characterized FUTs. b Secondary-structure conservation mapped onto the FUT8 catalytic domain for clade 1 FUTs. The heat map gradient (blue → red) reflects the degree of structural conservation, using FUT8 as the reference. To the right, a close-up view of the GDP-Fuc binding site highlights fully conserved and functionally analogous residues. c PROMALS3D-derived alignment²⁹⁷ of the C-terminal catalytic domains from human FUT1, FUT2, FUT8, POFUT1 and POFUT2 (UniProt IDs P19526, Q9BYC5, Q9H488, Q10981 and Q9Y2G5, respectively). Conserved secondary-structure elements are annotated as helices (h) or β-strands (e), and consensus positions are classified by residue properties. Fully conserved residues are indicated with black arrows, and residues with functional equivalence are marked with blue arrows. In the alignment, amino acid residues are color-coded by predicted secondary structure: red, α-helices; blue, β-strands; green, coil/loop regions. Consensus positions are classified by residue character: aliphatic (l), aromatic (@), hydrophobic (h), alcohol (o), polar (p), tiny (t), small (s), bulky (b), positively charged (+), negatively charged (–) and charged (c). Heat maps integrate experimental crystal structures when available and rely on predictive models otherwise. GDP-Fuc is rendered opaque when positioned from crystallographic data and semi-transparent when model-derived. For clarity of visualization, side chains located behind the ligand are displayed with partial transparency to avoid occlusion.