@article{c778e4c7-d1b8-4571-bbed-8ed06464b3f8,
  abstract     = {{Background: Inhibition of factor Xa (FXa) by tissue factor pathway inhibitor α (TFPIα) is potentiated by FV-Short and protein S. The C-terminus of TFPIα is important for formation of the TFPIα/protein S/FV-Short complex. It contains a hydrophobic sequence (LIKT). The purpose was to investigate the importance of the LIKT sequence.<br/><br/>Methods: Two TFPIα C-terminal peptides were synthesized, one wild-type and the other with LIKT replaced by AAKA. The effect of the peptides on TFPIα function was tested. An AAKA-mutant TFPIα was created and compared with wild-type TFPIα. AlphaFold was used to elucidate a mechanism for the role of the LIKT sequence.<br/><br/>Results: The wild-type peptide efficiently inhibited the FXa-inhibitory activity of TFPIα/protein S/FV-Short complex, whereas the AAKA peptide did not. The LIKT sequence in TFPIα was crucially important for the synergistic TFPIα-cofactor activity between protein S and FV-Short. AlphaFold (DeepMind, London, UK) suggested an interaction between LIKT and FV-Short B-loop 1510-1517 mediated through a network of hydrogen bonds and hydrophobic interactions.<br/><br/>Conclusions: The C-terminal TFPIα-peptide induced complex formation between protein S and FV-Short. The LIKT sequence in TFPIα was crucially important for the ability of protein S and FV-Short to function as synergistic TFPIα cofactors.}},
  author       = {{Dahlbäck, Björn and Tran, Sinh and Draczkowski, Piotr}},
  issn         = {{2785-5309}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{3}},
  series       = {{Bleeding, Thrombosis and Vascular Biology}},
  title        = {{The LIKT sequence in C-terminus of tissue factor pathway inhibitor (TFPIα) crucially important for the synergistic TFPIα-cofactor activity of protein S and FV-short}},
  url          = {{http://dx.doi.org/10.4081/btvb.2026.414}},
  doi          = {{10.4081/btvb.2026.414}},
  volume       = {{5}},
  year         = {{2026}},
}