PDBsum entry 2d3v

Immune system

PDB id: 2d3v

Contents

Protein chain

179 a.a. *

Waters ×105

* Residue conservation analysis

PDB id:

2d3v

Name:

Immune system

Title:

Crystal structure of leukocyte ig-like receptor a5 (lilra5/lir9/ilt11)

Structure:

Leukocyte immunoglobulin-like receptor subfamily a member 5 isoform 1. Chain: a. Fragment: extracellular domain. Synonym: leukocyte ig-like receptor a5 (lilra5/lir9/ilt11). Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.85Å R-factor: 0.235 R-free: 0.269

Authors:

M.Shiroishi,M.Kajikawa,K.Kuroki,T.Ose,D.Kohda,K.Maenaka

Key ref:

M.Shiroishi et al. (2006). Crystal structure of the human monocyte-activating receptor, "Group 2" leukocyte Ig-like receptor A5 (LILRA5/LIR9/ILT11). J Biol Chem, 281, 19536-19544. PubMed id: 16675463 DOI: 10.1074/jbc.M603076200

Date:

03-Oct-05 Release date: 06-Jun-06

Protein chain

A6NI73  (LIRA5_HUMAN) -  Leukocyte immunoglobulin-like receptor subfamily A member 5 from Homo sapiens

Seq: 299 a.a.

Struc: 179 a.a.

DOI no: 10.1074/jbc.M603076200

J Biol Chem 281:19536-19544 (2006)

PubMed id: 16675463

Crystal structure of the human monocyte-activating receptor, "Group 2" leukocyte Ig-like receptor A5 (LILRA5/LIR9/ILT11).

M.Shiroishi, M.Kajikawa, K.Kuroki, T.Ose, D.Kohda, K.Maenaka.

ABSTRACT

Human leukocyte Ig-like receptor B1 (LILRB1) and B2 (LILRB2) belong to "Group 1" receptors and recognize a broad range of major histocompatibility complex class I molecules (MHCIs). In contrast, "Group 2" receptors show low similarity with LILRB1/B2, and their ligands remain to be identified. To date, the structural and functional characteristics of Group 2 LILRs are poorly understood. Here we report the crystal structure of the extracellular domain of LILRA5, which is an activating Group 2 LILR expressed on monocytes and neutrophils. Unexpectedly, the structure showed large changes in structural conformation and charge distribution in the region corresponding to the MHCI binding site of LILRB1/B2, which are also distinct from killer cell Ig-like receptors and Fc alpha receptors. These changes probably confer the structural hindrance for the MHCI binding, and their key amino acid substitutions are well conserved in Group 2 LILRs. Consistently, the surface plasmon resonance and flow cytometric analyses demonstrated that LILRA5 exhibited no affinities to all tested MHCIs. These results raised the possibility that LILRA5 as well as Group 2 LILRs do not play a role in any MHCI recognition but could possibly bind to non-MHCI ligand(s) on the target cells to provide a novel immune regulation mechanism.

Selected figure(s)

Figure 1.
FIGURE 1. Crystal structure of the LILRA5 extracellular domain. A, ribbon drawing of the structure of LILRA5 in a rainbow color scheme from blue (N-terminal) to red (C-terminal). The dotted lines represent the disordered residues of loop regions (residues 106-116 and 136-138). The star indicates the predicted N-linked glycosylation site. B, topological diagram of LILRA5 structure. The arrows show the direction of the -strands. Cylinders labeled PP show polyproline II-type helices. C, left, overall view of domain 2 of LILRA5 (magenta) superimposed on LILRB1 (yellow). The region between 106 and 116 is disordered. Right, close-up view of the box in the left panel. LILRA5 and LILRB1 are shown in magenta and yellow stick models, respectively. Hydrogen bonds made between A' and G strands are shown in green dashed lines. The green dotted circle indicates the residue 105 following the disordered loop of LILRA5. The black dotted circle indicates the C-terminal residue of LILRA5 unable to form the A'GFCC' -sheet due to the distortion caused by Pro^194 (see text).

Figure 3.
FIGURE 3. Structural comparison of MHCI binding sites between LILRBs and LILRA5. A, center, the LILRB1 (light pink) of the HLA-A2 complex model (4) (heavy chain; blue, 2-microglobulin; cyan) is superimposed onto LILRA5 (red). Left and right, large structural difference observed in D1 (right, orange dotted circle around the C' strand) and D2 (right, blue dotted circle around the DE loop). LILRB1 (light pink) and LILRB2 (light green) are superimposed onto LILRA5 (red). B, the ribbon model of CC' sheet of LILRA5 (red) is superimposed onto those (C strand and 3[10] helices) of LILRB1 (light pink). Conserved amino acids are shown in a ball model (left), and their colors are the same as those in amino acid comparison among LILR members (right). Key amino acids for structural changes are colored, and this coloring is also applied in the labels in C. The characters, h and s, on the sequence alignment indicate helix and sheet structures, respectively. C, details of local structures around the 3[10] helix of LILRB1 (left) and C' sheet of LILRA5 (right), highlighted by the orange dotted circle in A. The black dotted lines are shown in order for the main-chain structures to be easily recognized. The hydrophobic core of LILRB1 (left) and hydrophobic pocket of LILRA5 (right) are indicated by the red dotted circles.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 19536-19544) copyright 2006.

Figures were selected by the author.

Author's comment

This paper describes the first crystal structure of "Group 2" Leukocyte Ig-like receptor, LILRA5.