PDBsum entry 3h8n

Immune system

PDB id: 3h8n

Contents

Protein chain

195 a.a. *

Waters ×53

* Residue conservation analysis

PDB id:

3h8n

Name:

Immune system

Title:

Crystal structure analysis of kir2ds4

Structure:

Killer cell immunoglobulin-like receptor 2ds4. Chain: a. Synonym: mhc class i nk cell receptor, natural killer-associated transcript 8, nkat-8, p58 natural killer cell receptor clone cl-39, p58 nk receptor, cl-17, cd158 antigen-like family member i. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cd158i, kir2ds4, kir2ds4 0010101, Kka3, nkat8. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å R-factor: 0.241 R-free: 0.284

Authors:

T.Graef,D.A.Bushnell,P.Parham

Key ref:

T.Graef et al. (2009). 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. PubMed id: 19858347

Date:

29-Apr-09 Release date: 20-Oct-09

Protein chain

P43632  (KI2S4_HUMAN) -  Killer cell immunoglobulin-like receptor 2DS4 from Homo sapiens

Seq: 304 a.a.

Struc: 195 a.a.

J Exp Med 206:2557-2572 (2009)

PubMed id: 19858347

KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C.

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.

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.