View source for 6aed


==Crystal Structure of the four Ig-like domain of LILRB2(LIR2/ILT4/CD85d)==
<StructureSection load='6aed' size='340' side='right'caption='[[6aed]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6aed]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AED OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AED FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.797&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6aed FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aed OCA], [https://pdbe.org/6aed PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aed RCSB], [https://www.ebi.ac.uk/pdbsum/6aed PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aed ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LIRB2_HUMAN 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.<ref>PMID:9548455</ref> <ref>PMID:9842885</ref> <ref>PMID:11875462</ref> <ref>PMID:12853576</ref> 
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== 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<ref>PMID:31273318</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6aed" style="background-color:#fffaf0;"></div>

==See Also==
*[[Leukocyte immunoglobulin-like receptor|Leukocyte immunoglobulin-like receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gao GF]]
[[Category: Qi J]]
[[Category: Song H]]
[[Category: Wang Q]]