 |
PDBsum entry 4csy
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion
|
PDB id
|
|
|
|
4csy
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Cell adhesion
|
|
|
Title:
|
|
E-selectin lectin, egf-like and two scr domains complexed with sialyl lewis x
|
|
Structure:
|
|
E-selectin. Chain: a, b. Fragment: lectin domain, egf-like domain, short consensus repeat domain 1, short consensus repeat domain 2, residues 22-301. Synonym: cd62 antigen-like family member e, endothelial leukocyte adhesion molecule 1, elam-1, leukocyte-endothelial cell adhesion molecule 2, lecam2. Engineered: yes. Other_details: n-acetylglucosamine residues attached to asn4, asn124,
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Tissue: cytokine-induced vascular endothelial cells. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: chinese hamster ovary (cho) cells. Expression_system_tissue: ovary.
|
|
Resolution:
|
|
|
2.41Å
|
R-factor:
|
0.217
|
R-free:
|
0.253
|
|
|
Authors:
|
|
R.C.Preston,R.P.Jakob,F.P.C.Binder,C.P.Sager,B.Ernst,T.Maier
|
|
Key ref:
|
|
R.C.Preston
et al.
(2016).
E-selectin ligand complexes adopt an extended high-affinity conformation.
J Mol Cell Biol,
8,
62-72.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
11-Mar-14
|
Release date:
|
24-Sep-14
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P16581
(LYAM2_HUMAN) -
E-selectin from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
610 a.a.
280 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
J Mol Cell Biol
8:62-72
(2016)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
E-selectin ligand complexes adopt an extended high-affinity conformation.
|
|
R.C.Preston,
R.P.Jakob,
F.P.Binder,
C.P.Sager,
B.Ernst,
T.Maier.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes
essential leukocyte rolling in the early inflammatory response by binding to
glycoproteins containing the tetrasaccharide sialyl Lewis(x) (sLe(x)). Efficient
leukocyte recruitment under vascular flow conditions depends on an increased
lifetime of E-selectin/ligand complexes under tensile force in a so-called
catch-bond binding mode. Co-crystal structures of a representative fragment of
the extracellular E-selectin region with sLe(x) and a glycomimetic antagonist
thereof reveal an extended E-selectin conformation, which is identified as a
high-affinity binding state of E-selectin by molecular dynamics simulations.
Small-angle X-ray scattering experiments demonstrate a direct link between
ligand binding and E-selectin conformational transition under static conditions
in solution. This permits tracing a series of concerted structural changes
connecting ligand binding to conformational stretching as the structural basis
of E-selectin catch-bond-mediated leukocyte recruitment. The detailed molecular
view of the binding site paves the way for the design of a new generation of
selectin antagonists. This is of special interest, since their therapeutic
potential was recently demonstrated with the pan-selectin antagonists GMI-1070
(Rivipansel).
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
