Mode of Interaction between β2GPI and Lipoprotein Receptors Suggests Mutually Exclusive Binding of β2GPI to the Receptors and Anionic Phospholipids

Chang Jin Lee, Alfredo De Biasio, Natalia Beglova

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.
Original languageEnglish (US)
Pages (from-to)366-376
Number of pages11
JournalStructure
Volume18
Issue number3
DOIs
StatePublished - Mar 10 2010
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2022-09-13

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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