PDBsum entry 3h8n

Immune system

PDB id: 3h8n

Contents

Protein chain

195 a.a.

Waters ×53

References listed in PDB file

Key reference

• Title: Kir2ds4 is a product of gene conversion with kir3dl2 that introduced specificity for hla-A11 While diminishing avidity for hla-C.
• Authors: T.Graef, A.K.Moesta, P.J.Norman, L.Abi-Rached, L.Vago, A.M.Older aguilar, M.Gleimer, J.A.Hammond, L.A.Guethlein, D.A.Bushnell, P.J.Robinson, P.Parham.
• Ref.: J Exp Med, 2009, 206, 2557-2572.
• PubMed id: 19858347

Abstract

Human killer cell immunoglobulin-like receptors (KIRs) are distinguished by expansion of activating KIR2DS, whose ligands and functions remain poorly understood. The oldest, most prevalent KIR2DS is KIR2DS4, which is represented by a variable balance between "full-length" and "deleted" forms. We find that full-length 2DS4 is a human histocompatibility leukocyte antigen (HLA) class I receptor that binds specifically to subsets of C1+ and C2+ HLA-C and to HLA-A*11, whereas deleted 2DS4 is nonfunctional. Activation of 2DS4+ NKL cells was achieved with A*1102 as ligand, which differs from A*1101 by unique substitution of lysine 19 for glutamate, but not with A*1101 or HLA-C. Distinguishing KIR2DS4 from other KIR2DS is the proline-valine motif at positions 71-72, which is shared with KIR3DL2 and was introduced by gene conversion before separation of the human and chimpanzee lineages. Site-directed swap mutagenesis shows that these two residues are largely responsible for the unique HLA class I specificity of KIR2DS4. Determination of the crystallographic structure of KIR2DS4 shows two major differences from KIR2DL: displacement of contact loop L2 and altered bonding potential because of the substitutions at positions 71 and 72. Correlation between the worldwide distributions of functional KIR2DS4 and HLA-A*11 points to the physiological importance of their mutual interaction.