7KHF

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

7KHF の概要

• エントリーDOI: 10.2210/pdb7khf/pdb
• 関連するPDBエントリー: 7KFK
• EMDBエントリー: 22879
• 分子名称: MDB1 Fab heavy chain, MDB1 Fab light chain, Rifin, ... (5 entities in total)
• 機能のキーワード: lilrb1, rifin, malaria, receptor-inserted antibody, mdb1, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 171491.72

構造登録者

Xu, K.,Kwong, P.D. (登録日: 2020-10-21, 公開日: 2021-03-31, 最終更新日: 2024-10-16)

主引用文献

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, P.D.,Geiger, R.,Sallusto, F.,Kwong, P.D.,Lanzavecchia, A.
Structural basis of malaria RIFIN binding by LILRB1-containing antibodies.
Nature, 592:639-643, 2021

PubMed 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 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.

PubMed: 33790470
DOI: 10.1038/s41586-021-03378-6

実験手法

ELECTRON MICROSCOPY (3.54 Å)