PDBsum entry 2kri

Protein binding/endocytosis

PDB id: 2kri

Contents

Protein chains

82 a.a. *

38 a.a. *

Metals

_CA

* Residue conservation analysis

PDB id:

2kri

Name:

Protein binding/endocytosis

Title:

Structure of a complex between domain v of beta2-glycoprotein i and the fourth ligand-binding module from ldlr determined with haddock

Structure:

Beta-2-glycoprotein 1. Chain: a. Fragment: sushi-like domain. Synonym: beta-2-glycoprotein i, beta(2)gpi, b2gpi, apolipoprotein h, apo-h, activated protein c-binding protein, apc inhibitor, anticardiolipin cofactor. Engineered: yes. Low-density lipoprotein receptor. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: apoh, b2g1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ldlr.

NMR struc:

1 models

Authors:

N.Beglova

Key ref:

C.J.Lee et al. (2010). Mode of interaction between beta2GPI and lipoprotein receptors suggests mutually exclusive binding of beta2GPI to the receptors and anionic phospholipids. Structure, 18, 366-376. PubMed id: 20223219

Date:

18-Dec-09 Release date: 31-Mar-10

Protein chain

P02749  (APOH_HUMAN) -  Beta-2-glycoprotein 1 from Homo sapiens

Seq: 345 a.a.

Struc: 82 a.a.*

Protein chain

P01130  (LDLR_HUMAN) -  Low-density lipoprotein receptor from Homo sapiens

Seq: 860 a.a.

Struc: 38 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Structure 18:366-376 (2010)

PubMed id: 20223219

Mode of interaction between beta2GPI and lipoprotein receptors suggests mutually exclusive binding of beta2GPI to the receptors and anionic phospholipids.

C.J.Lee, A.De Biasio, N.Beglova.

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.