6AEE

Crystal structure of the four Ig-like domains of LILRB1 complexed with HLA-G


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and HLA-G1 complex.

Wang, Q.Song, H.Cheng, H.Qi, J.Nam, G.Tan, S.Wang, J.Fang, M.Shi, Y.Tian, Z.Cao, X.An, Z.Yan, J.Gao, G.F.

(2019) Cell Mol Immunol 

  • DOI: https://doi.org/10.1038/s41423-019-0258-5
  • Primary Citation of Related Structures:  
    6AED, 6AEE

  • PubMed Abstract: 

    Leukocyte immunoglobulin (Ig)-like receptors (LILRs), also known as CD85 and immunoglobulin-like transcripts (ILTs), play pivotal roles in regulating immune responses. These receptors define an immune checkpoint that immune therapy can target. Through cis or trans interactions with human leukocyte antigen (HLA)-G, the two most abundantly expressed inhibitory LILRs, LILRB1, and LILRB2 (LILRB1/2, also known as CD85j/d and ILT2/4), are involved in immunotolerance in pregnancy and transplantation, autoimmune diseases, and immune evasion by tumors. Although the discrete domains of LILRB1/2 are clear, the assembly mode of the four extracellular Ig-like domains (D1, D2, D3, and D4) remains unknown. Previous data indicate that D1D2 is responsible for binding to HLA class I (HLA-I), but the roles of D3D4 are still unclear. Here, we determined the crystal structure of the four Ig-like domain LILRB2 and four-domain LILRB1 in complex with HLA-G1. The angles between adjacent domains and the staggered assembly of the four domains suggest limited flexibility and limited plasticity of the receptors during ligand binding. The complex structure of four-domain LILRB1 and HLA-G1 supports the model that D1D2 is responsible for HLA-I binding, while D3D4 acts as a scaffold. Accordingly, cis and trans binding models for HLA-I binding to LILRB1/2 are proposed. The geometries of LILRB1/2 in complex with dimeric and monomeric HLA-G1 suggest the accessibility of the dimeric receptor, which in turn, transduces more inhibitory signals. The assembly of LILRB1/2 and its binding to HLA-G1 could aid in the design of immune regulators and benefit immune interference.


  • Organizational Affiliation

    CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. wangqihui@im.ac.cn.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, alpha chain G
A, D
277Homo sapiensMutation(s): 3 
Gene Names: HLA-G
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PHAROS:  P17693
GTEx:  ENSG00000204632 
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UniProt GroupP17693
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, E
100Homo sapiensMutation(s): 0 
Gene Names: B2M
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Find proteins for P61769 (Homo sapiens)
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PHAROS:  P61769
GTEx:  ENSG00000166710 
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
9 Mer Peptide (RL9) From Histone H2A.x
C, F
9Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Leukocyte immunoglobulin-like receptor subfamily B member 1
G, H
399Homo sapiensMutation(s): 0 
Gene Names: LILRB1
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Find proteins for Q8NHL6 (Homo sapiens)
Explore Q8NHL6 
Go to UniProtKB:  Q8NHL6
PHAROS:  Q8NHL6
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UniProt GroupQ8NHL6
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.683α = 90
b = 154.681β = 102.24
c = 98.198γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-07-31
    Type: Initial release
  • Version 1.1: 2023-11-22
    Changes: Data collection, Database references, Refinement description