Structure of Natural Killer Cell Receptor 2B4 (CD244) bound to its Ligand, CD48

VELIKOVSKY A; DENG L; CHLEWICKI L; FERNÁNDEZ M; KUMAR V; MARIUZZA RA

IMMUNITY

Cell Press

Año: 2007 vol. 27 p. 572 - 584

1074-7613

Abstract Natural killer (NK) cells play a vital role in eliminating virally infected and tumor cells. Among the receptors regulating NK cell function is 2B4 (CD244), a member of the signaling lymphocyte activation molecule (SLAM) family that interacts with CD48. 2B4 is the only heterophilic receptor of the SLAM family, whose other members (e.g. NTBA) are self-ligands. To understand heterophilic recognition within the SLAM family, we determined the structure of the complex between N-terminal domains of mouse 2B4 and CD48, as well as the structures of unbound 2B4 and CD48. The complex reveals an association mode related to, yet distinct from, that of the NTB-A dimer. Binding is accompanied by rigidification of flexible regions of 2B4 containing most of the polymorphic residues across different species and receptor isoforms. We propose a model for 2B4–CD48 interactions that permits intermixing of SLAM receptors with MHCspecific receptors in the NK cell immune synapse.