PDBsum entry 1p4l

Immune system

PDB id: 1p4l

Contents

Protein chains

273 a.a. *

99 a.a. *

122 a.a. *

Ligands

SER-ILE-ILE-ASN-PHE-GLU-LYS-LEU

* Residue conservation analysis

PDB id:

1p4l

Name:

Immune system

Title:

Crystal structure of nk receptor ly49c mutant with its mhc class i ligand h-2kb

Structure:

Mhc class i h-2kb heavy chain. Chain: a. Fragment: extracellular alpha-1, alpha-2, alpha-3. Synonym: h-2 class i histocompatibility antigen, k-b alpha chain, h- 2kb. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: h2-k. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.90Å R-factor: 0.269 R-free: 0.295

Authors:

J.Dam,R.Guan,K.Natarajan,N.Dimasi,R.A.Mariuzza

Key ref:

J.Dam et al. (2003). Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b). Nat Immunol, 4, 1213-1222. PubMed id: 14595439 DOI: 10.1038/ni1006

Date:

23-Apr-03 Release date: 11-Nov-03

Protein chain

P01901  (HA1B_MOUSE) -  H-2 class I histocompatibility antigen, K-B alpha chain from Mus musculus

Seq: 369 a.a.

Struc: 273 a.a.

Protein chain

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

Seq: 119 a.a.

Struc: 99 a.a.

Protein chain

Q64329  (KLRA3_MOUSE) -  Killer cell lectin-like receptor 3 from Mus musculus

Seq: 266 a.a.

Struc: 122 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/ni1006

Nat Immunol 4:1213-1222 (2003)

PubMed id: 14595439

Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b).

J.Dam, R.Guan, K.Natarajan, N.Dimasi, L.K.Chlewicki, D.M.Kranz, P.Schuck, D.H.Margulies, R.A.Mariuzza.

ABSTRACT

The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes.

Selected figure(s)

Figure 2.
Figure 2. Structure of Ly49/MHC class I complexes. (a) Superposition of wild-type (blue) and mutant (red) Ly49C -H-2Kb complexes in the crystallographic asymmetric unit, indicating close overall similarity. (b) Electron density in the interface of the mutant Ly49C -H-2Kb complex. The F[o] - F[c] omit map at 2.9 Å resolution is contoured at 2.5 . Ly49C residues 239 -243 (red), H-2Kb heavy chain residues 111 -117 (blue) and [2]M residues 58 -60 (yellow) were excluded from the map calculation. (c) Ribbon diagram of the mutant Ly49C -H-2Kb complex, in which the crystallographic Ly49C dimer (red) crosslinks two MHC class I molecules. (d) Structure of the Ly49A -H-2D^d complex, showing the asymmetric interaction between the Ly49A dimer (green) and two MHC class I molecules. The two interaction surfaces, site 1 and site 2, are indicated by the dashed circle and rectangle, respectively. In c and d, the H-2Kb heavy chain is blue, the ovalbumin peptide (ball-and-stick representation) is red and [2]M is yellow.

Figure 6.
Figure 6. Comparison of hydrogen-bonding networks at the Ly49C -H-2Kb and Ly49A -H-2D^d interfaces. (a) Detailed view (stereo diagram) of the Ly49C -H-2Kb interface showing hydrogen bonds (dotted black lines) between Ly49C (red) and the H-2Kb heavy chain (blue) or [2]M (violet); the side chains of interacting residues are yellow. The portion of the Ly49C L3 loop, encompassing residues 226 -231, which is disordered in both mutant and wild-type structures, is drawn arbitrarily (red balls). With the exception of H-2Kb residues Asp212 and Thr214, whose side chains could potentially interact with the disordered L3 loop of Ly49C, only residues forming hydrogen bonds are shown. (b) Stereo diagram showing hydrogen bonds between Ly49A (green) and the H-2D^d heavy chain (blue) or [2]M (violet) at the site 2 interface of the Ly49A -H-2D^d complex.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2003, 4, 1213-1222) copyright 2003.

Figures were selected by an automated process.