Lipoprotein receptors of the LDLR family serve as clearance receptors for β2GPI and as signaling receptors for the β2GPI/antibody complexes in antiphospholipid syndrome. We compared four ligand-binding LA modules from LDLR and ApoER2 for their ability to bind domain V of β2GPI (β2GPI-DV). We found that the LA modules capable of binding β2GPI-DV interact with the same region on β2GPI-DV using residues at their calcium-coordination site. The structure of a complex between β2GPI-DV and LA4 of LDLR, solved by molecular docking guided by NMR-derived restraints and extensively validated, represents the general mode of interaction between β2GPI and lipoprotein receptors. We have shown that β2GPI-DV cannot simultaneously bind to lipoprotein receptors and anionic phospholipids, suggesting that the association of β2GPI/anti-β2GPI antibody complexes with anionic phospholipids will interfere with lipoprotein receptors' signaling in APS. © 2010 Elsevier Ltd. All rights reserved.
Bibliographical noteGenerated from Scopus record by KAUST IRTS on 2022-09-13
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology