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Yorodumi- PDB-7kfk: Crystal structure of LILRB1 D3D4 domain in complex with Plasmodiu... -
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-Basic information
Entry | Database: PDB / ID: 7kfk | ||||||
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Title | Crystal structure of LILRB1 D3D4 domain in complex with Plasmodium RIFIN (PF3D7_1373400) V2 domain | ||||||
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Keywords | IMMUNE SYSTEM / LILRB1 / RIFIN / Malaria | ||||||
Function / homology | Function and homology information HLA-A specific inhibitory MHC class I receptor activity / positive regulation of gamma-delta T cell activation involved in immune response / MHC class Ib protein complex binding / HLA-B specific inhibitory MHC class I receptor activity / negative regulation of dendritic cell differentiation / immune response-inhibiting cell surface receptor signaling pathway / MHC class Ib protein binding / Fc receptor mediated inhibitory signaling pathway / negative regulation of mononuclear cell proliferation / MHC class Ib receptor activity ...HLA-A specific inhibitory MHC class I receptor activity / positive regulation of gamma-delta T cell activation involved in immune response / MHC class Ib protein complex binding / HLA-B specific inhibitory MHC class I receptor activity / negative regulation of dendritic cell differentiation / immune response-inhibiting cell surface receptor signaling pathway / MHC class Ib protein binding / Fc receptor mediated inhibitory signaling pathway / negative regulation of mononuclear cell proliferation / MHC class Ib receptor activity / negative regulation of T cell mediated cytotoxicity / MHC class I receptor activity / negative regulation of CD8-positive, alpha-beta T cell activation / negative regulation of transforming growth factor beta production / negative regulation of alpha-beta T cell activation / negative regulation of cytokine production involved in immune response / negative regulation of serotonin secretion / dendritic cell differentiation / protein phosphatase 1 binding / negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / negative regulation of osteoclast development / negative regulation of interleukin-12 production / negative regulation of interferon-beta production / negative regulation of endocytosis / negative regulation of dendritic cell apoptotic process / positive regulation of macrophage cytokine production / T cell proliferation involved in immune response / negative regulation of natural killer cell mediated cytotoxicity / negative regulation of interleukin-10 production / negative regulation of calcium ion transport / negative regulation of type II interferon production / negative regulation of tumor necrosis factor production / negative regulation of cell cycle / regulation of immune response / MHC class I protein binding / positive regulation of defense response to virus by host / negative regulation of T cell proliferation / SH2 domain binding / response to virus / receptor internalization / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of type II interferon production / defense response to virus / cellular response to lipopolysaccharide / adaptive immune response / membrane => GO:0016020 / positive regulation of apoptotic process / external side of plasma membrane / positive regulation of gene expression / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular region / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Plasmodium falciparum (malaria parasite P. falciparum) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.63 Å | ||||||
Authors | Xu, K. / Kwong, P.D. | ||||||
Citation | Journal: Nature / Year: 2021 Title: Structural basis of malaria RIFIN binding by LILRB1-containing antibodies. Authors: Yiwei Chen / Kai Xu / Luca Piccoli / Mathilde Foglierini / Joshua Tan / Wenjie Jin / Jason Gorman / Yaroslav Tsybovsky / Baoshan Zhang / Boubacar Traore / Chiara Silacci-Fregni / Claudia ...Authors: Yiwei Chen / Kai Xu / Luca Piccoli / Mathilde Foglierini / Joshua Tan / Wenjie Jin / Jason Gorman / Yaroslav Tsybovsky / Baoshan Zhang / Boubacar Traore / Chiara Silacci-Fregni / Claudia Daubenberger / Peter D Crompton / Roger Geiger / Federica Sallusto / Peter D Kwong / Antonio Lanzavecchia / Abstract: Some Plasmodium falciparum repetitive interspersed families of polypeptides (RIFINs)-variant surface antigens that are expressed on infected erythrocytes-bind to the inhibitory receptor LAIR1, and ...Some Plasmodium falciparum repetitive interspersed families of polypeptides (RIFINs)-variant surface antigens that are expressed on infected erythrocytes-bind to the inhibitory receptor LAIR1, and insertion of DNA that encodes LAIR1 into immunoglobulin genes generates RIFIN-specific antibodies. Here we address the general relevance of this finding by searching for antibodies that incorporate LILRB1, another inhibitory receptor that binds to β2 microglobulin and RIFINs through their apical domains. 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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PDBx/mmCIF format | 7kfk.cif.gz | 144.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7kfk.ent.gz | 110.5 KB | Display | PDB format |
PDBx/mmJSON format | 7kfk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kf/7kfk ftp://data.pdbj.org/pub/pdb/validation_reports/kf/7kfk | HTTPS FTP |
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-Related structure data
Related structure data | 7khfC 4llaS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
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-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
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