7khf

CryoEM structure of LILRB1 D3D4 domain-inserted antibody MDB1 Fab in complex with Plasmodium RIFIN (PF3D7_1373400) V2 domain

spinqualitylabelsall models 7khf, resolution 3.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7khf is a 6 chain structure with sequence from Homo sapiens and Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.54Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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