PDBsum entry 3cad

Unknown function

PDB id: 3cad

Contents

Protein chains

123 a.a. *

Waters ×70

* Residue conservation analysis

PDB id:

3cad

Name:

Unknown function

Title:

Crystal structure of natural killer cell receptor, ly49g

Structure:

Lectin-related nk cell receptor ly49g1. Chain: a, b. Fragment: ly49g. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: klra7. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.60Å R-factor: 0.230 R-free: 0.286

Authors:

S.Cho

Key ref:

L.Deng et al. (2008). Molecular architecture of the major histocompatibility complex class I-binding site of Ly49 natural killer cell receptors. J Biol Chem, 283, 16840-16849. PubMed id: 18426793 DOI: 10.1074/jbc.M801526200

Date:

19-Feb-08 Release date: 08-Apr-08

Protein chains

Q60654  (KLRA7_MOUSE) -  Killer cell lectin-like receptor 7 from Mus musculus

Seq: 280 a.a.

Struc: 123 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1074/jbc.M801526200

J Biol Chem 283:16840-16849 (2008)

PubMed id: 18426793

Molecular architecture of the major histocompatibility complex class I-binding site of Ly49 natural killer cell receptors.

L.Deng, S.Cho, E.L.Malchiodi, M.C.Kerzic, J.Dam, R.A.Mariuzza.

ABSTRACT

Natural killer (NK) cells play a vital role in the detection and destruction of virally infected and tumor cells during innate immune responses. The highly polymorphic Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex class I (MHC-I) molecules on target cells. Despite the determination of two Ly49-MHC-I complex structures, the molecular features of Ly49 receptors that confer specificity for particular MHC-I alleles have not been identified. To understand the functional architecture of Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and completed refinement of the Ly49C-H-2K(b) complex. This information, combined with mutational analysis of Ly49A, permitted a structure-based classification of Ly49s that we used to dissect the binding site into three distinct regions, each having different roles in MHC recognition. One region, located at the center of the binding site, has a similar structure across the Ly49 family and mediates conserved interactions with MHC-I that contribute most to binding. However, the preference of individual Ly49s for particular MHC-I molecules is governed by two regions that flank the central region and are structurally more variable. One of the flanking regions divides Ly49s into those that recognize both H-2D and H-2K versus only H-2D ligands, whereas the other discriminates among H-2D or H-2K alleles. The modular design of Ly49-binding sites provides a framework for predicting the MHC-binding specificity of Ly49s that have not been characterized experimentally.

Selected figure(s)

Figure 2.
FIGURE 2. Structure of the Ly49C-H-2K^b complex. A, ribbon diagram of the Ly49C-H-2K^b complex. Domains are labeled. The 1, 2, and 3 domains of the MHC-I heavy chain are green; β[2]mis orange; the MHC-bound peptide in ball-and-stick representation is gray; the Ly49C dimer is rose. B, composite omit electron density map (dark green, contoured at 1.5 ) of Ly49C-H-2K^b at 2.90 Å resolution, showing residues 218-226 of Ly49C helix 3. C, structural rearrangements in Ly49C induced by binding to MHC-I. Bound Ly49C is rose; unbound Ly49C is gold; H-2K^b is green. Salt bridges are indicated by solid lines.

Figure 3.
FIGURE 3. Comparison of Ly49-MHC-I interfaces. A, Ly49C-H-2K^b interface, highlighting interactions made by residues 211-231 of Ly49C. B, Ly49A-H-2D^d complex, showing interactions made by the corresponding region of Ly49A. Domains are labeled. The side chains of interacting residues are drawn in ball-and-stick representation, with carbon atoms in rose (Ly49C), cyan (Ly49A), green (H-2K^b or H-2D^d), or orange (β[2]m), and oxygen atoms in red, nitrogen atoms in blue, and sulfur in yellow. Salt bridges and hydrogen bonds are represented by solid and dotted lines, respectively.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 16840-16849) copyright 2008.

Figures were selected by an automated process.