6aed

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Crystal Structure of the four Ig-like domain of LILRB2(LIR2/ILT4/CD85d)

Structural highlights

6aed is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.797Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LIRB2_HUMAN Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Involved in the down-regulation of the immune response and the development of tolerance. Competes with CD8A for binding to class I MHC antigens. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.[1] [2] [3] [4]

Publication Abstract from PubMed

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.

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 GF Cell Mol Immunol. 2019 Jul 4. pii: 10.1038/s41423-019-0258-5. doi:, 10.1038/s41423-019-0258-5. PMID:31273318[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
11 reviews cite this structure
The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?
Attia et al. (2020)
10 more
10 other articles
No citations found

See Also

References

  1. ↑ Borges L, Hsu ML, Fanger N, Kubin M, Cosman D. A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules. J Immunol. 1997 Dec 1;159(11):5192-6. PMID:9548455
  2. ↑ Fanger NA, Cosman D, Peterson L, Braddy SC, Maliszewski CR, Borges L. The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes. Eur J Immunol. 1998 Nov;28(11):3423-34. PMID:9842885
  3. ↑ Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, Lederman S, Colonna M, Cortesini R, Dalla-Favera R, Suciu-Foca N. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol. 2002 Mar;3(3):237-43. Epub 2002 Jan 28. PMID:11875462 doi:10.1038/ni760
  4. ↑ Shiroishi M, Tsumoto K, Amano K, Shirakihara Y, Colonna M, Braud VM, Allan DS, Makadzange A, Rowland-Jones S, Willcox B, Jones EY, van der Merwe PA, Kumagai I, Maenaka K. Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8856-61. Epub 2003 Jul 9. PMID:12853576 doi:10.1073/pnas.1431057100
  5. ↑ 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 GF. Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and HLA-G1 complex. Cell Mol Immunol. 2019 Jul 4. pii: 10.1038/s41423-019-0258-5. doi:, 10.1038/s41423-019-0258-5. PMID:31273318 doi:http://dx.doi.org/10.1038/s41423-019-0258-5

Contents


PDB ID 6aed

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OCA

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