PDBsum entry 1qub

Membrane adhesion

PDB id: 1qub

Contents

Protein chain

319 a.a. *

Ligands

NAG-NAG-MAN

NAG-NAG

NAG ×2

Waters ×32

* Residue conservation analysis

PDB id:

1qub

Name:

Membrane adhesion

Title:

Crystal structure of the glycosylated five-domain human beta2- glycoprotein i purified from blood plasma

Structure:

Protein (human beta2-glycoprotein i). Chain: a. Fragment: beta2-glycoprotein i

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organelle: blood plasma

Biol. unit:

Dimer (from PQS)

Resolution:

2.70Å R-factor: 0.249 R-free: 0.269

Authors:

B.Bouma,P.G.De Groot,J.M.H.Van Den Elsen,R.B.G.Ravelli,A.Schouten, M.J.A.Simmelink,R.H.W.M.Derksen,J.Kroon,P.Gros

Key ref:

B.Bouma et al. (1999). Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure. EMBO J, 18, 5166-5174. PubMed id: 10508150 DOI: 10.1093/emboj/18.19.5166

Date:

01-Jul-99 Release date: 08-Oct-99

Protein chain

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

Seq: 345 a.a.

Struc: 319 a.a.

DOI no: 10.1093/emboj/18.19.5166

EMBO J 18:5166-5174 (1999)

PubMed id: 10508150

Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure.

B.Bouma, P.G.de Groot, J.M.van den Elsen, R.B.Ravelli, A.Schouten, M.J.Simmelink, R.H.Derksen, J.Kroon, P.Gros.

ABSTRACT

Human beta(2)-glycoprotein I is a heavily glycosylated five-domain plasma membrane-adhesion protein, which has been implicated in blood coagulation and clearance of apoptotic bodies from the circulation. It is also the key antigen in the autoimmune disease anti-phospholipid syndrome. The crystal structure of beta(2)-glycoprotein I isolated from human plasma reveals an elongated fish-hook-like arrangement of the globular short consensus repeat domains. Half of the C-terminal fifth domain deviates strongly from the standard fold, as observed in domains one to four. This aberrant half forms a specific phospholipid-binding site. A large patch of 14 positively charged residues provides electrostatic interactions with anionic phospholipid headgroups and an exposed membrane-insertion loop yields specificity for lipid layers. The observed spatial arrangement of the five domains suggests a functional partitioning of protein adhesion and membrane adhesion over the N- and C-terminal domains, respectively, separated by glycosylated bridging domains. Coordinates are in the Protein Data Bank (accession No. 1QUB).

Selected figure(s)

Figure 1.
Figure 1 Structural representations of human blood plasma 2GPI revealing the extended chain of the five SCR domains. (A) Ribbon drawing of 2GPI with consecutive domains labelled I -V. N-linked glycans, as well as the position of the putative O-linked glycan, Thr130, are indicated by a ball-and-stick model. -strands are shown in red and helices in green. (B) Topology diagram of 2GPI. The central -sheets of all five domains are labelled B2(-B2")-B3-B4(-B5), the N- and C-terminal -sheets are labelled B1'-B2' and B4'-B5', the -helix and the 3/10 helix are denoted A1 and A2 and numbers of residues delimiting secondary structure elements are given. Disulfide bonds are indicated with dashed lines. The positions of N-glycosylation are given by hexagons; a diamond indicates the putative O-glycan. Horizontal dashed lines mark domain boundaries. (C) Ribbon representation of domain III of 2GPI with labelled secondary structure elements. The two fully conserved disulfide bonds are shown in yellow. (D) Ribbon representation of domain V of 2GPI with labelled secondary structure elements. The three disulfide bonds are indicated with yellow lines. The aberrant face, which contains the membrane-binding site, is located on the right-hand side.

Figure 5.
Figure 5 Binding of 2GPI to an anionic phospholipid surface. (A) Two views, related by 180° rotation, of the electrostatic potential surface of 2GPI. Domains are labelled I -V. The electrostatic potential is scaled from red for negative to blue for positive. (B) Positively charged patch on the aberrant half of domain V. The 14 residues contributing to this patch and the position of the disordered loop Ser311 -Lys317 are indicated. (C) Diagram of the proposed model for binding of 2GPI to acidic phospholipids. The positively charged patch on the surface of domain V is indicated by '+', acidic phospholipids are depicted by '-' and the putative membrane-insertion loop Ser311 -Ser -Leu -Ala -Phe -Trp -Lys317 is shown to insert into the phospholipid layer. The positions of N-glycans are indicated by hexagons and the putative site for O-linked glycosylation is indicated by a diamond.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 5166-5174) copyright 1999.

Figures were selected by the author.