Poster Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

In-depth conformational study of the von Willebrand Factor D' domain using molecular dynamics simulations (#244)

Vishal Pandya , Ineke Muir , Steve Dower , Tiffany Walsh

von Willebrand factor (vWF) is a blood protein that plays a pivotal role in hemostasis. The vWF-D' region comprises two regions, TIL' and E', that are indicated as the principal regions for binding to Factor VIII.1 The molecular structure of vWF-D' has been recently revealed by NMR experiments,2 suggesting TIL' to have higher flexibility compared to the E' region. The flexibility of TIL' is of interest due to the presence of numerous sites for type 2N mutation in this region. Here, we present an in-depth conformational study of the vWF-TIL'-E' region. Our analysis indicates that TIL' can access many more conformations relative to E', consistent with NMR data, due to the lack of substantive intra-peptide interactions in TIL'. Our structural model provides a platform for future computational mutation studies in vWF-D', to aid the interpretation of experimental mutation and binding studies.

  1. 1) Y-F. Zhou, E. T. Eng, J. Zhu, C. Lu, T. Walz and T. A. Springer, 
Blood, 2012, 120, 449–458. 

  2. 2) N. Shiltagh, J. Kirkpatrick, L. D. Cabrita, T. A. J. McKinnon, K. Thalassinos, E. G. D. Tuddenham and D. F. Hansen, Blood, 2014, 123, 4143–4151.