Project Details
Projekt
Zentralprojekt
Applicant
Professor Dr. Reinhard Schneppenheim
Subject Area
Biophysics
Term
from 2011 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 172540668
Von Willebrand factor (VWF) is an adhesive, multi-functional huge multimerized protein with multiple domains harboring binding sites for collagen, platelet glycoprotein receptors GPib and GPIIb/llla, and coagulation factor VIII (FVIII). The functional domains enable VWF to bind to the injured vessel wall, to recruit platelets to the site of injury by adhesion and aggregation and to bind and protect FVIII, an important cofactor of the coagulation cascade. VWF function in primary hemostasis is strictly correlating with its multimer size. ln this project we will continue to express and purify all recombinant proteins necessary for the research projects of our partners within SHENC. These proteins include the wildtype and mutated variations of full-length VWF, selected single VWF domains and domain assemblies with and without mutations, and VWF binding proteins like platelet GPib and Gpllb/llla as weil as the VWF cleaving protease ADAMTS13. Additionally we will clone, express and purify novel VWF peptides and mutants upon demand of our partners within SHENC, which can also be produced with individually requested tags. We will further perform quality control of the produced proteins by activity tests to assess their structural and functional properties. The produced proteins will then be used by the SHENG consortium to investigate I) the shear force regulation of interactions between VWF and known and novel binding partners, II) kinetics of VWF cleavage by ADAMTS 13, III) physiological relevance of formation of VWF containing collective networks under normal and inflammatory conditions, V) VWF-domain crystallography, and VI) effects of genetic variations on VWF function.
DFG Programme
Research Units
