C3 - STAFF C3 - RESEARCH C3 - PUBLICATIONS
     
  
  
        
 

The main field of expertise of the Wilmanns group is in high-resolution structural biology, by making use of high brilliance synchrotron radiation. In the SHENC network, our first research aim addresses the C terminal stem region of VWF which has a crucial role in both protein network formation by integrin binding and in maintaining and potentially regulating the global architecture of the protein under different cellular environmental conditions.

We aim using structural biology to address the important question of what the functional roles of the C domains are in mediating network formation and how do specific amino acid polymorphisms in the C domain array (A1/Schneppenheim) perturb the normal function of VWF proteins?

Our second research aim focuses on the A domain region of VWF that is the most extensively characterized region of VWF and a number of high-resolution structures have been determined. Despite this, there are still unanswered questions as to how the A1-domain generates specificity for the distinct range of protein targets it has been proposed to interact with such as GPIb, collagen subtypes and in an auto-regulatory mechanism, the A2-domain.

We aim to quantitatively and structurally characterize this A1-A2 interaction using biophysical methods and X-ray crystallography. We expect that these data will explain how the interaction between A domains and mutations in these domains influences the regulation of GPIb and collagen binding. We believe that high resolution structural information will contribute to existing hypotheses generated by SHENC partners in the first funding period and reveal crucial factors involved in VWF function.

 
        
  
  
 
     
C3 - STAFF C3 - RESEARCH C3 - PUBLICATIONS