Identification of an E-Selectin Region Critical for Carbohydrate Recognition and Cell Adhesion

E-selectin elicits cell adhesion by binding to the cell surface carbohydrate, sialyl Lewis X ( sLex). We evaluated the effects of mutations in the E-selectin lectin domain on the binding of a panel of anti-E-selectin mAbs and on the recognition of immobilized sLexglycolipid. Functional residues were then superimposed onto a three-dimensional model of the E-selectin lectin domain. This analysis demonstrated that the epitopes recognized by blocking mAbs map to a patch near the antiparallel beta sheet derived from the NH2and COOH termini of the lectin domain and two adjacent loops. Mutations that affect sLexbinding map to this same region. These results thus define a small region of the E-selectin lectin domain that is critical for carbohydrate recognition.