 |
PDBsum entry 2pf6
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion
|
PDB id
|
|
|
|
2pf6
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Cell adhesion
|
|
|
Title:
|
|
Lutheran glycoprotein, n-terminal domains 1 and 2
|
|
Structure:
|
|
Lutheran blood group glycoprotein. Chain: a, b. Fragment: n-terminal domains 1 and 2. Synonym: b-cam cell surface glycoprotein, auberger b antigen, f8/g253 antigen, cd239 antigen. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: bcam, lu, msk19.
|
|
Resolution:
|
|
|
2.20Å
|
R-factor:
|
0.207
|
R-free:
|
0.251
|
|
|
Authors:
|
|
N.Burton,R.L.Brady
|
|
Key ref:
|
|
T.J.Mankelow
et al.
(2007).
The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3.
Blood,
110,
3398-3406.
PubMed id:
|
|
|
Date:
|
|
|
04-Apr-07
|
Release date:
|
04-Dec-07
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P50895
(BCAM_HUMAN) -
Basal cell adhesion molecule from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
628 a.a.
231 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Blood
110:3398-3406
(2007)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3.
|
|
T.J.Mankelow,
N.Burton,
F.O.Stefansdottir,
F.A.Spring,
S.F.Parsons,
J.S.Pedersen,
C.L.Oliveira,
D.Lammie,
T.Wess,
N.Mohandas,
J.A.Chasis,
R.L.Brady,
D.J.Anstee.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The Lutheran blood group glycoprotein, first discovered on erythrocytes, is
widely expressed in human tissues. It is a ligand for the alpha5 subunit of
Laminin 511/521, an extracellular matrix protein. This interaction may
contribute to vaso-occlusive events that are an important cause of morbidity in
sickle cell disease. Using x-ray crystallography, small-angle x-ray scattering,
and site-directed mutagenesis, we show that the extracellular region of Lutheran
forms an extended structure with a distinctive bend between the second and third
immunoglobulin-like domains. The linker between domains 2 and 3 appears to be
flexible and is a critical determinant in maintaining an overall conformation
for Lutheran that is capable of binding to Laminin. Mutagenesis studies indicate
that Asp312 of Lutheran and the surrounding cluster of negatively charged
residues in this linker region form the Laminin-binding site. Unusually,
receptor binding is therefore not a function of the domains expected to be
furthermost from the plasma membrane. These studies imply that structural
flexibility of Lutheran may be essential for its interaction with Laminin and
present a novel opportunity for the development of therapeutics for sickle cell
disease.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
D.J.Anstee
(2011).
The functional importance of blood group-active molecules in human red blood cells.
|
| |
Vox Sang,
100,
140-149.
|
|
|
|
|
|
|
N.M.Burton,
and
G.Daniels
(2011).
Structural modelling of red cell surface proteins.
|
| |
Vox Sang,
100,
129-139.
|
|
|
|
|
|
|
D.Hatherley,
S.C.Graham,
K.Harlos,
D.I.Stuart,
and
A.N.Barclay
(2009).
Structure of signal-regulatory protein alpha: a link to antigen receptor evolution.
|
| |
J Biol Chem,
284,
26613-26619.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
D.J.Anstee
(2009).
Red cell genotyping and the future of pretransfusion testing.
|
| |
Blood,
114,
248-256.
|
|
|
|
|
|
|
J.A.Chasis,
and
N.Mohandas
(2008).
Erythroblastic islands: niches for erythropoiesis.
|
| |
Blood,
112,
470-478.
|
|
|
|
|
|
|
X.An,
E.Gauthier,
X.Zhang,
X.Guo,
D.J.Anstee,
N.Mohandas,
and
J.A.Chasis
(2008).
Adhesive activity of Lu glycoproteins is regulated by interaction with spectrin.
|
| |
Blood,
112,
5212-5218.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
|
Links
