PDBsum entry 1efx

Immune system

PDB id: 1efx

Contents

Protein chains

278 a.a. *

100 a.a. *

197 a.a. *

Ligands

GLY-ALA-VAL-ASP-PRO-LEU-LEU-ALA-LEU

Waters ×185

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of an nk cell immunoglobulin-Like receptor in complex with its class i mhc ligand.

Authors

J.C.Boyington, S.A.Motyka, P.Schuck, A.G.Brooks, P.D.Sun.

Ref.

Nature, 2000, 405, 537-543. [DOI no: 10.1038/35014520]

PubMed id

10850706

Abstract

Target cell lysis is regulated by natural killer (NK) cell receptors that recognize class I MHC molecules. Here we report the crystal structure of the human immunoglobulin-like NK cell receptor KIR2DL2 in complex with its class I ligand HLA-Cw3 and peptide. KIR binds in a nearly orthogonal orientation across the alpha1 and alpha2 helices of Cw3 and directly contacts positions 7 and 8 of the peptide. No significant conformational changes in KIR occur on complex formation. The receptor footprint on HLA overlaps with but is distinct from that of the T-cell receptor. Charge complementarity dominates the KIR/HLA interface and mutations that disrupt interface salt bridges substantially diminish binding. Most contacts in the complex are between KIR and conserved HLA-C residues, but a hydrogen bond between Lys 44 of KIR2DL2 and Asn 80 of Cw3 confers the allotype specificity. KIR contact requires position 8 of the peptide to be a residue smaller than valine. A second KIR/HLA interface produced an ordered receptor-ligand aggregation in the crystal which may resemble receptor clustering during immune synapse formation.

Figure 2.
Figure 2: The KIR2DL2/HLA-Cw3 interface. a, Charge complementarity at the interface. Basic residues are dark blue, acidic residues are red, and the remaining residues are coloured by molecule. b,c, Stereo view of the interaction between domain D1 of KIR, the GAV peptide and the 1 helix of HLA-Cw3 (b), and domain D2 of KIR, the hinge loop, the GAV peptide and the 2 helix of HLA-Cw3 (c). KIR is shown in light blue, the GAV peptide in purple and HLA-Cw3 in green. Selected hydrogen bonds are represented by dotted lines.

Figure 5.
Figure 5: KIR/HLA aggregation. The complex of KIR2DL2 and HLA-Cw3 forms a regular oligomeric aggregate in the crystal lattice. KIR and HLA-Cw3 are shown in green and orange, respectively. The functional and oligomeric KIR/HLA-Cw3 interfaces are highlighted in pink and grey, respectively. The predicted glycosylation sites (highlighted by blue dots) are at residues 63, 157 and 190 for KIR, and at 86 for HLA-Cw3.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 405, 537-543) copyright 2000.

Secondary reference #1

Title

Crystal structure of the hla-Cw3 allotype-Specific killer cell inhibitory receptor kir2dl2.

Authors

G.A.Snyder, A.G.Brooks, P.D.Sun.

Ref.

Proc Natl Acad Sci U S A, 1999, 96, 3864-3869. [DOI no: 10.1073/pnas.96.7.3864]

PubMed id

10097129

Figure 1.
Fig. 1. (A) Ribbon diagram of 2DL2 structure. The secondary structure assignment for the strands in D1 domain are A (8-12), A' (16-19), B (23-30), C (36-43), C' (46-52), D (53-56), E (60-67), F (75-82), and G (90-101). The strands for the D2 domain are: A (108-111), A' (116-119), B (123-130), C (135-142), C' (145-152), D (153-156), E (160-167), F (172-180), and G (188-198), respectively. This figure and other structural figures were prepared by using the program MOLSCRIPT 2.1 and RASTER3D (55, 56). The region around cis-Pro-14 (B) and cis-Pro-114 (C) shows the kink at the proline residue and the -hairpin.

Figure 2.
Fig. 2. (A) Stereo drawing showing the structure overlay between 2DL1 (in red) and 2DL2 (in green) with their D2 domains superimposed. The hinge angles, calculated with the program HINGE, are 66° and 80° for 2DL1 and 2DL2, respectively. Residues involved in the interdomain packing are shown. The coordinates are from the refined orthorhombic crystal form. (B) Overlay of refined 2DL2 structures from the orthorhombic (in green) and the trigonal (in blue) crystal forms.