 |
PDBsum entry 2ceh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Blood clotting
|
PDB id
|
|
|
|
2ceh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Spectroscopic characterization of successive phosphorylation of the tissue factor cytoplasmic region.
|
|
|
Authors
|
|
M.Sen,
M.Herzik,
J.W.Craft,
A.L.Creath,
S.Agrawal,
W.Ruf,
G.B.Legge.
|
|
|
Ref.
|
|
Open Spectrosc J, 2009,
3,
58-64.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Tissue Factor (TF) is well known for its role during the activation of the
coagulation pathway, but it is also critical for tumor biology and inflammation
through protease activated receptor (PAR) 2 signaling. This signaling function
is modulated by the successive phosphorylation of residues Ser253 and Ser258
within the TF cytoplasmic region (TFCR). This paper reports how we used NMR and
spectroscopic methods to investigate the structural propensities of the
unphosphorylated and phosphorylated forms of the TFCR. When unphosphorylated,
the TFCR forms a local hydrophobic collapse around Trp254 and an electropositive
patch from the membrane proximal basic block (Arg246-Lys247) to the conserved
PKCalpha consensus residue Lys255. Phosphorylation of Ser253 alters the charge
characteristics of this membrane proximal region, thereby strengthening the
interaction between residue Ala248 and the Trp254 aromatic group.
Phosphorylation of the Ser258-Pro259 motif destabilizes a turn at the C-terminus
to form an extended polyproline helical motif. Our data suggests that by
changing both its charge and local structural propensity, covalent modifications
of the TFCR can potentially regulate its association with the cellular membrane
and its signaling partners.
|
|
|
|
|
|
|
