Our research builds upon 30+ years of continuously funded work on the enzymology and structural biology of proteins involved in blood coagulation and on mechanisms of ligand binding.

We are interested in the structural enzymology of proteins responsible for blood coagulation, with the goal of unraveling the molecular architecture and mechanism of the underlying interactions. Our approach uses a combination of conventional (rapid kinetics, protein engineering, X-ray crystallography) and innovative (smFRET, cryo-EM) biophysical techniques.

We currently focus on the interaction of prothrombin with prothrombinase, leading to generation of thrombin and blood clotting, the activation of factor V required for assembly of prothrombinase and the interaction of the thrombin-thrombomodulin complex with protein C that halts the coagulation response. Current studies also focus on factor V short and its interactions with TFPIalpha, protein S and factor Xa. Emerging interests include proteins of the contact pathway like factors IX, XI and XII.

Ongoing Research

  1. Structure and dynamics of prothrombin (HL049413)
  2. Structural enzymology of protein C (HL139554)
  3. Structural enzymology of factor V activation (HL147821)

Video showing the complex of prothrombin (yellow), fVa (green), and fXa (red).

Read more about the Di Cera Lab’s plenary paper in Blood here: Blood 2022.

Selected Recent Publications

Mohammed BM, Pelc LA, Rau MJ and Di Cera E. Cryo-EM structure of coagulation factor V short. (2023) Blood. Pubmed Blood
Stojanovski BM and Di Cera E. Monitoring prothrombin activation in plasma through loss of Förster resonance energy transfer. (2023) J Thromb Haemost. Pubmed J Thromb Haemost
Stojanovski BM and Di Cera E. Comparative sequence analysis of vitamin K-dependent coagulation factors. (2022) J Thromb Haemost. 20, 2837-2849 Pubmed J Thromb Haemost PMC Article
Di Cera E, Mohammed BM, Pelc LA and Stojanovski BM. Cryo-EM structures of coagulation factors. (2022) Res Pract Thromb Haemost. 6, e12830 Pubmed Res Pract Thromb Haemost PMC Article
Ruben EA, Summers B, Rau MJ, Fitzpatrick JAJ and Di Cera E. Cryo-EM structure of the prothrombin-prothrombinase complex. (2022) Blood. 139, 3463-3473 Pubmed Blood PMC Article
Pelc LA, Koester SK, Kukla CR, Chen Z and Di Cera E. The active site region plays a critical role in Na binding to thrombin. (2022) J Biol Chem. 298, 101458 Pubmed J Biol Chem PMC Article
Stojanovski BM and Di Cera E. Role of sequence and position of the cleavage sites in prothrombin activation. (2021) J Biol Chem. 297, 100955 Pubmed J Biol Chem PMC Article
Ruben EA, Rau MJ, Fitzpatrick JAJ and Di Cera E. Cryo-EM structures of human coagulation factors V and Va. (2021) Blood. 137, 3137-3144 Pubmed Blood PMC Article

Complete Bibliography via PubMed: Di Cera E