DETERMINATION OF THE SOLUTION STRUCTURE OF A PLATELET-ADHESION PEPTIDE OF VONWILLEBRAND-FACTOR

Two-dimensional nuclear magnetic resonance (NMR) spectroscopy in combination with distance geometry (DG) and dynamical simulated annealing (DSA) calculations have been used to determine the tertiary solution structure of a synthetic 29-residue fragment of von Willebrand factor (vWF). This fragment (D514-E542) represents an adhesion site on vWF for its platelet receptor, the glycoprotein Ib-IX complex (GP Ib-IX). The NMR data yielded 109 interproton distance measurements and two chi1 dihedral angle constraints for use in DG and DSA calculations. Most prominent in the calculated family of solution structures was an amphipathic, right-handed alpha-helix in the C-terminal segment of the peptide. We propose that this highly structured region may be important for the specific molecular interaction of vWF with the GP Ib-IX complex.