2CEH

Phosphorylation of the Cytoplasmic Tail of Tissue Factor and its Role in Modulating Structure and Binding Affinity

2CEH の概要

• エントリーDOI: 10.2210/pdb2ceh/pdb
• 関連するPDBエントリー: 1AHW 1BOY 1DAN 1FAK 1J9C 1JPS 1NL8 1O5D 1TFH 1UJ3 1W0Y 1W2K 1WQV 1WSS 1WTG 1WUN 1WV7 1Z6J 2C4F 2CEF 2HFT
• NMR情報: BMRB: 6991
• 分子名称: TISSUE FACTOR (1 entity in total)
• 機能のキーワード: unphosphorylated, pin1, ww domain, blood coagulation, glycoprotein, lipoprotein, palmitate, polymorphism, transmembrane, coagulation protein, blood clotting
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2063.32

構造登録者

Sen, M.,Agrawal, S.,Craft, J.W.,Ruf, W.,Legge, G.B. (登録日: 2006-02-06, 公開日: 2007-02-13, 最終更新日: 2024-05-15)

主引用文献

Sen, M.,Herzik, M.,Craft, J.W.,Creath, A.L.,Agrawal, S.,Ruf, W.,Legge, G.B.
Spectroscopic Characterization of Successive Phosphorylation of the Tissue Factor Cytoplasmic Region.
Open Spectrosc.J., 3:58-, 2009

PubMed 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.

PubMed: 20076769
DOI: 10.2174/1874383800903010058

実験手法

SOLUTION NMR