Structure-based modeling of the ligand binding domain of the human cell surface receptor CD23 and comparison of two independently derived molecular models

Abstract

CD23, a type II membrane receptor protein, recognizes four different ligands via its extracellular C‐type lectin domain: immunoglobulin E (IgE), CD21, and the β2‐integrins CD11b and CD11c. CD23 specifically interacts in a calcium‐dependent manner, “lectin‐like” with carbohydrate moieties expressed on CD21 and CD11b/c, but also “lectin‐unlike” with protein epitopes on IgE. As a first step in analyzing the multiple binding specificities associated with CD23 in more detail, we report a detailed molecular model of the lectin‐like domain of human CD23 (hCD23). The model was built based on information provided by X‐ray structures of mannose binding protein (MBP) and E‐selectin, both of which are members of the calcium‐dependent (C‐type) lectin superfamily. Sequence‐structure comparisons suggest that hCD23 is structurally more similar to MBP than to E‐selectin. The hCD23 model is compared to an independently derived model. Although the CD23‐carbohydrate and CD23‐protein interactions are both calcium dependent, analysis of the model suggests the presence of distinct binding sites for these ligands.