Crystal structure of the C-type lectin-like domain from the human hematopoietic cell receptor CD69

CD69,: one of the earliest specific antigens acquired during lymphoid activation, acts as a signal-transducing receptor,involved in cellular activation events, including proliferation and induction of specific genes. CD69 belongs:to a family of receptors that modulate the immune response and whose genes are clustered in the natural killer (NK) gene complex. The extracellular portion of these receptors represent a subfamily of C-type lectin-like domains (CTLDs), which are divergent from true C-type lectins and are referred to as NK-cell domains (NKDs). We have determined the three-dimensional:Structure of human CD69 NKD in two different crystal forms. CD69 NKD adopts the canonical CTLD fold but lacks:the features involved in Ca2+ and carbohydrate binding by C-type lectins. CD69 NKD dimerizes noncovalently, both in solution and in crystalline state. The dimer interface consists of a hydrophobic, loosely packed core,:surrounded by polar interactions, including an interdomain beta sheet. The intersubunit core shows certain structural plasticity that may facilitate conformational: rearrangements for binding to ligands. The surface equivalent to the binding site of other members of the CTLD superfamily reveals a hydrophobic patch surrounded by conserved charged residues that probably constitutes:the CD69 ligand-binding site.