View source for 7kfk


==Crystal structure of LILRB1 D3D4 domain in complex with Plasmodium RIFIN (PF3D7_1373400) V2 domain==
<StructureSection load='7kfk' size='340' side='right'caption='[[7kfk]], [[Resolution|resolution]] 2.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kfk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KFK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KFK 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]] 2.63&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7kfk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kfk OCA], [https://pdbe.org/7kfk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kfk RCSB], [https://www.ebi.ac.uk/pdbsum/7kfk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kfk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LIRB1_HUMAN LIRB1_HUMAN] Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of the signal triggered by FCER1A and inhibits serotonin release. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.<ref>PMID:9285411</ref> <ref>PMID:9842885</ref> <ref>PMID:11907092</ref> 
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== Publication Abstract from PubMed ==
Some Plasmodium falciparum repetitive interspersed families of polypeptides (RIFINs)-variant surface antigens that are expressed on infected erythrocytes(1)-bind to the inhibitory receptor LAIR1, and insertion of DNA that encodes LAIR1 into immunoglobulin genes generates RIFIN-specific antibodies(2,3). Here we address the general relevance of this finding by searching for antibodies that incorporate LILRB1, another inhibitory receptor that binds to beta2 microglobulin and RIFINs through their apical domains(4,5). By screening plasma from a cohort of donors from Mali, we identified individuals with LILRB1-containing antibodies. B cell clones isolated from three donors showed large DNA insertions in the switch region that encodes non-apical LILRB1 extracellular domain 3 and 4 (D3D4) or D3 alone in the variable-constant (VH-CH1) elbow. Through mass spectrometry and binding assays, we identified a large set of RIFINs that bind to LILRB1 D3. Crystal and cryo-electron microscopy structures of a RIFIN in complex with either LILRB1 D3D4 or a D3D4-containing antibody Fab revealed a mode of RIFIN-LILRB1 D3 interaction that is similar to that of RIFIN-LAIR1. The Fab showed an unconventional triangular architecture with the inserted LILRB1 domains opening up the VH-CH1 elbow without affecting VH-VL or CH1-CL pairing. Collectively, these findings show that RIFINs bind to LILRB1 through D3 and illustrate, with a naturally selected example, the general principle of creating novel antibodies by inserting receptor domains into the VH-CH1 elbow.

Structural basis of malaria RIFIN binding by LILRB1-containing antibodies.,Chen Y, Xu K, Piccoli L, Foglierini M, Tan J, Jin W, Gorman J, Tsybovsky Y, Zhang B, Traore B, Silacci-Fregni C, Daubenberger C, Crompton PD, Geiger R, Sallusto F, Kwong PD, Lanzavecchia A Nature. 2021 Apr;592(7855):639-643. doi: 10.1038/s41586-021-03378-6. Epub 2021 , Mar 31. PMID:33790470<ref>PMID:33790470</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 7kfk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Leukocyte immunoglobulin-like receptor|Leukocyte immunoglobulin-like receptor]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Kwong PD]]
[[Category: Xu K]]