2CFJ
Phosphorylation of the Cytoplasmic Tail of Tissue Factor and its Role in Modulating Structure and Binding Affinity
Summary for 2CFJ
| Entry DOI | 10.2210/pdb2cfj/pdb |
| Related | 1AHW 1BOY 1DAN 1FAK 1J9C 1JPS 1NL8 1O5D 1TFH 1UJ3 1W0Y 1W2K 1WQV 1WSS 1WTG 1WUN 1WV7 1Z6J 2B7D 2C4F 2CEF 2CEH 2CEZ 2HFT |
| NMR Information | BMRB: 6998 |
| Descriptor | TISSUE FACTOR (1 entity in total) |
| Functional Keywords | pin1, ww domain, phosphorylation, blood coagulation, glycoprotein, lipoprotein, palmitate, transmembrane, blood clotting |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 2143.30 |
| Authors | Sen, M.,Agrawal, S.,Craft, J.W.,Ruf, W.,Legge, G.B. (deposition date: 2006-02-21, release date: 2007-03-20, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 20076769DOI: 10.2174/1874383800903010058 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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