PDBsum entry 1qo3

Receptor/immune system

PDB id: 1qo3

Contents

Protein chains

274 a.a. *

100 a.a. *

128 a.a. *

121 a.a. *

Ligands

ARG-GLY-PRO-GLY-ARG-ALA-PHE-VAL-THR-ILE

EDO ×3

Waters ×352

* Residue conservation analysis

PDB id:

1qo3

Name:

Receptor/immune system

Title:

Complex between nk cell receptor ly49a and its mhc class i ligand h- 2dd

Structure:

Mhc class i h-2dd heavy chain. Chain: a. Fragment: extracellular domain. Synonym: h-2 class i histocompatibility antigen, d-d alpha chain, (h- 2d(d)). Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: b2m.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Strain: balb/c. Cell: most nucleated cells. Cellular_location: cell surface. Gene: h-2d. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Biol. unit:

Pentamer (from PDB file)

Resolution:

2.30Å R-factor: 0.198 R-free: 0.238

Authors:

J.Tormo,R.A.Mariuzza

Key ref:

J.Tormo et al. (1999). Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. Nature, 402, 623-631. PubMed id: 10604468 DOI: 10.1038/45170

Date:

01-Nov-99 Release date: 02-Jan-00

Protein chain

P01900  (HA12_MOUSE) -  H-2 class I histocompatibility antigen, D-D alpha chain from Mus musculus

Seq: 365 a.a.

Struc: 274 a.a.

Protein chain

P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus

Seq: 119 a.a.

Struc: 100 a.a.*

Protein chain

P20937  (KLRA1_MOUSE) -  T-cell surface glycoprotein YE1/48 from Mus musculus

Seq: 262 a.a.

Struc: 128 a.a.*

Protein chain

P20937  (KLRA1_MOUSE) -  T-cell surface glycoprotein YE1/48 from Mus musculus

Seq: 262 a.a.

Struc: 121 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1038/45170

Nature 402:623-631 (1999)

PubMed id: 10604468

Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand.

J.Tormo, K.Natarajan, D.H.Margulies, R.A.Mariuzza.

ABSTRACT

Natural killer (NK) cell function is regulated by NK receptors that interact with MHC class I (MHC-I) molecules on target cells. The murine NK receptor Ly49A inhibits NK cell activity by interacting with H-2D(d) through its C-type-lectin-like NK receptor domain. Here we report the crystal structure of the complex between the Ly49A NK receptor domain and unglycosylated H-2D(d). The Ly49A dimer interacts extensively with two H-2D(d) molecules at distinct sites. At one interface, a single Ly49A subunit contacts one side of the MHC-I peptide-binding platform, presenting an open cavity towards the conserved glycosylation site on the H-2D(d) alpha2 domain. At a second, larger interface, the Ly49A dimer binds in a region overlapping the CD8-binding site. The smaller interface probably represents the interaction between Ly49A on the NK cell and MHC-I on the target cell, whereas the larger one suggests an interaction between Ly49A and MHC-I on the NK cell itself. Both Ly49A binding sites on MHC-I are spatially distinct from that of the T-cell receptor.

Selected figure(s)

Figure 1.
Figure 1 Structure of the Ly49A/H-2D^d complex and the interaction sites. a, Stereo diagram of the complex and crystal packing interactions. View shows the asymmetric interaction between an Ly49A dimer and two H-2D^d molecules related by the crystal symmetry. The H-2D^d heavy chain is yellow, [2]m is grey, and the two Ly49A subunits, Ly49A-1 and Ly49A-2, are cyan and blue, respectively, whereas the viral peptide is shown in orange ball-and-stick representation. The two interaction surfaces, site 1 and site 2, are indicated by a red circle and a black rectangle, respectively. b, c, Detailed view of site 1 showing the interactions using a common orientation based on the 'standard' view for the MHC-I molecule. c, Close up of the interactions at site 1. The view has been rotated around the horizontal relative to b and depicts the region highlighted by a box. d, e, As in b, c but for site 2. The two domains of the MHC-I peptide-binding platform are shown in cream ( 1) and dark yellow ( 2). Hydrogen bonds between Ly49A and H-2D^d are depicted as broken lines. All figures were drawn using programs BOBSCRIPT49 and Raster3D^50.

Figure 5.
Figure 5 The putative carbohydrate-binding pocket at the Ly49A/H-2D^d interface. A close-up of the complex interface at site 1 is shown, centred at the open cavity around N176, a conserved glycosylation site in rodent MHC-I molecules. The orientation and the polypeptide chain representation are as in Fig. 1b. Two proximal carbohydrates, a GlcNAc and a fucose residue, have been modelled on the basis of crystal structures of MHC-I molecules deposited in the Protein Data Bank. The carbohydrate residues (pink) and surrounding amino-acid side chains (cyan for Ly49A and yellow for H-2D^d) are shown in ball-and-stick representation; the branching fucose residue could fit well into the deep open pocket. The red arrow indicates position 4 in the GluNAc residue where the rest of the oligosaccharide is attached, and which can establish further interactions along the flat surface of the Ly49A dimer (Fig. 1b).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1999, 402, 623-631) copyright 1999.

Figures were selected by the author.