Research

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 two basic interactions of the blood coagulation cascade, i.e., the interaction of prothrombin with prothrombinase leading to generation of thrombin and blood clotting, and the interaction of the thrombin-thrombomodulin complex with protein C that shuts down the coagulation response.

Our goal is to solve the molecular architecture of prothrombin and protein C, free and bound to their biological activators, and to gain information on the underlying dynamics, mechanism of activation, and epitopes involved in the interactions.

Our approach uses a combination of conventional (rapid kinetics, protein engineering, X-ray crystallography, NMR) and state-of-the-art (smFRET, cryo-EM) biophysical techniques.

Ongoing Research

  1. Structure and dynamics of prothrombin (HL049413)
  2. Structural enzymology of protein C (HL139554)
  3. Molecular determinants of thrombin allostery (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.

Recent Publications

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
Di Cera E. Mechanisms of ligand binding. (2020) Biophys Rev (Melville). 1, 011303 Pubmed Biophys Rev (Melville) PMC Article
Stojanovski BM, Pelc LA, Zuo X and Di Cera E. Zymogen and activated protein C have similar structural architecture. (2020) J Biol Chem. 295, 15236-15244 Pubmed J Biol Chem PMC Article
Stojanovski BM, Pelc LA and Di Cera E. Role of the activation peptide in the mechanism of protein C activation. (2020) Sci Rep. 10, 11079 Pubmed Sci Rep PMC Article
Ruben EA, Gandhi PS, Chen Z, Koester SK, DeKoster GT, Frieden C and Di Cera E. F NMR reveals the conformational properties of free thrombin and its zymogen precursor prethrombin-2. (2020) J Biol Chem. 295, 8227-8235 Pubmed J Biol Chem PMC Article

Complete Bibliography via PubMed: Di Cera E