1auq
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A1 DOMAIN OF VON WILLEBRAND FACTOR
OverviewOverview
von Willebrand Factor (vWF) is a multimeric protein that mediates platelet, adhesion to exposed subendothelium at sites of vascular injury under, conditions of high flow/shear. The A1 domain of vWF (vWF-A1) forms the, principal binding site for platelet glycoprotein Ib (GpIb), an interaction, that is tightly regulated. We report here the crystal structure of the, vWF-A1 domain at 2.3-A resolution. As expected, the overall fold is, similar to that of the vWF-A3 and integrin I domains. However, the, structure also contains N- and C-terminal arms that wrap across the lower, surface of the domain. Unlike the integrin I domains, vWF-A1 does not, contain a metal ion-dependent adhesion site motif. Analysis of the, available mutagenesis data suggests that the activator botrocetin binds to, the right-hand face of the domain containing helices alpha5 and alpha6., Possible binding sites for GpIb are the front and upper surfaces of the, domain. Natural mutations that lead to constitutive GpIb binding (von, Willebrand type IIb disease) cluster in a different site, at the interface, between the lower surface and the terminal arms, suggesting that they, disrupt a regulatory region rather than forming part of the primary GpIb, binding site. A possible pathway for propagating structural changes from, the regulatory region to the ligand-binding surface is discussed.
DiseaseDisease
Known diseases associated with this structure: von Willebrand disease OMIM:[193400]
About this StructureAbout this Structure
1AUQ is a Single protein structure of sequence from Homo sapiens with IUM as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib., Emsley J, Cruz M, Handin R, Liddington R, J Biol Chem. 1998 Apr 24;273(17):10396-401. PMID:9553097
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