Crystal Structure of the C-type Lectin-like Domain from the Human Hematopoietic Celol Receptor CD69

LLERA ANDREA S; VIEDMA FERNANDO; SÁNCHEZ MADRID FRANCISCO; TORMO, J

JOURNAL OF BIOLOGICAL CHEMISTRY

Año: 2001 vol. 276 p. 7312 - 7319

0021-9258

CD69, one of the earliest specific antigens acquiredduring lymphoid activation, acts as a signal-transducingreceptor involved in cellular activation events, includingproliferation and induction of specific genes. CD69belongs to a family of receptors that modulate the immuneresponse and whose genes are clustered in thenatural killer (NK) gene complex. The extracellular portionof these receptors represent a subfamily of C-typelectin-like domains (CTLDs), which are divergent fromtrue C-type lectins and are referred to as NK-cell domains(NKDs). We have determined the three-dimensionalstructure of human CD69 NKD in two differentcrystal forms. CD69 NKD adopts the canonical CTLDfold but lacks the features involved in Ca21 and carbohydratebinding by C-type lectins. CD69 NKD dimerizesnoncovalently, both in solution and in crystalline state.The dimer interface consists of a hydrophobic, looselypacked core, surrounded by polar interactions, includingan interdomain b sheet. The intersubunit core showscertain structural plasticity that may facilitate conformationalrearrangements for binding to ligands. Thesurface equivalent to the binding site of other membersof the CTLD superfamily reveals a hydrophobic patchsurrounded by conserved charged residues that probablyconstitutes the CD69 ligand-binding site.