Understanding the mechanism of blood-clotting protein binding is crucial to the continued development of treatments for blood coagulation disorders. The blood-clotting cascade is initiated when Factor VIIa (FVIIa) binds to human tissue factor (TF), a 29 kDa membrane protein. Here, the nanocrystalline and membrane-bound forms of TF are investigated with solid-state NMR. A suite of multidimensional solid-state NMR experiments has been acquired in order to complete the chemical shift assignments of the extracellular domain of TF. These chemical shifts agree well with the previously published solution NMR and X-ray crystal data, and provide new information about residues missing in the highest resolution X-ray crystal structure. Studies on full length, Nanodisc-incorporated TF indicate that TF retains the beta-sheet secondary structure of the extracellular domain upon membrane binding; however, perturbations are observed in several regions proximal to the TF/FVIIa putative exosite near the membrane surface.

Elucidating the structure and functional dynamics of membrane-bound tissue factor by solid-state NMR

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.