 |
PDBsum entry 1qub
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Membrane adhesion
|
PDB id
|
|
|
|
1qub
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Adhesion mechanism of human beta(2)-Glycoprotein i to phospholipids based on its crystal structure.
|
|
|
Authors
|
|
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.
|
|
|
Ref.
|
|
EMBO J, 1999,
18,
5166-5174.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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).
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
