title: Mode of interaction between beta2GPI and lipoprotein receptors suggests mutually exclusive binding of beta2GPI to the receptors and anionic phospholipids.
abstract: Lipoprotein receptors of the LDLR family serve as clearance receptors for beta2GPI and as signaling receptors for the beta2GPI/antibody complexes in antiphospholipid syndrome. We compared four ligand-binding LA modules from LDLR and ApoER2 for their ability to bind domain V of beta2GPI (beta2GPI-DV). We found that the LA modules capable of binding beta2GPI-DV interact with the same region on beta2GPI-DV using residues at their calcium-coordination site. The structure of a complex between beta2GPI-DV and LA4 of LDLR, solved by molecular docking guided by NMR-derived restraints and extensively validated, represents the general mode of interaction between beta2GPI and lipoprotein receptors. We have shown that beta2GPI-DV cannot simultaneously bind to lipoprotein receptors and anionic phospholipids, suggesting that the association of beta2GPI/anti-beta2GPI antibody complexes with anionic phospholipids will interfere with lipoprotein receptors' signaling in APS.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Chang-Jin
authors.initials: CJ
authors.lastname: Lee
authors.forename: Alfredo
authors.initials: A
authors.lastname: De Biasio
authors.forename: Natalia
authors.initials: N
authors.lastname: Beglova
mesh_terms: D001665:Binding Sites; D008024:Ligands; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000737:chemistry* / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D046912:Multiprotein Complexes; D010743:Phospholipids; D018110:Receptors, Lipoprotein; D053482:beta 2-Glycoprotein I