3H8N

Crystal Structure Analysis of KIR2DS4

Summary for 3H8N

• Entry DOI: 10.2210/pdb3h8n/pdb
• Related: 1efx 1im9
• Descriptor: Killer cell immunoglobulin-like receptor 2DS4 (2 entities in total)
• Functional Keywords: ligand-binding domains, cell membrane, disulfide bond, glycoprotein, immunoglobulin domain, membrane, polymorphism, receptor, transmembrane, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P43632
• Total number of polymer chains: 1
• Total formula weight: 21534.24

Authors

Graef, T.,Bushnell, D.A.,Parham, P. (deposition date: 2009-04-29, release date: 2009-10-20, Last modification date: 2024-10-09)

Primary citation

Graef, T.,Moesta, A.K.,Norman, P.J.,Abi-Rached, L.,Vago, L.,Older Aguilar, A.M.,Gleimer, M.,Hammond, J.A.,Guethlein, L.A.,Bushnell, D.A.,Robinson, P.J.,Parham, P.
KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C.
J.Exp.Med., 206:2557-2572, 2009

PubMed 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.

PubMed: 19858347
DOI: 10.1084/jem.20091010

Experimental method

X-RAY DIFFRACTION (2.5 Å)