Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding

摘要: Abstract Background: Bleeding from a damaged blood vessel is stopped by the formation of platelet plug. The multimeric plasma glycoprotein, von Willebrand factor (vWF), plays an essential role in this process anchoring platelets to wall under conditions high shear stress. This mediates adhesion binding both collagen and glycoprotein Ib on membrane. A3 domain vWF allows it bind types I III present perivascular connective tissue wall. To gain insight into mechanism vWF, we have determined crystal structure human domain. Results: 20 kDa (residues 920–1111), method multiwavelength anomalous dispersion at 1.8 A resolution, exhibits common dinucleotide-binding fold. putative collagen-binding site rather smooth shows markedly concentration negatively charged residues. region encompasses potential metal-binding containing motif DXSXS, which required for ligand interaction homologous I-type domains integrins CR3 LFA-1. Although has considerable sequence structural similarity with LFA-1 region, one loop adopts conformation incompatible ion binding. Conclusions: suggests that primarily achieved through interactions between residues positively collagen. absence pronounced groove precludes large van der Waals surface consistent low affinity single requirement tight association bound metal ions upon soaking MgCl 2 A3's conformational incompatibility functional A3, contrasts activation integrin domains.