title: The von willebrand factor A3 domain does not contain a metal ion-dependent adhesion site motif.
abstract: von Willebrand factor (vWF) is a multimeric plasma protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury. The A3 domain of vWF (vWF-A3) forms the principal binding site for collagens type I and III. We report here the crystal structure of the vWF-A3 domain at 2.2-A resolution. As expected, the structure is similar to the integrin I domain but with several novel features. Sequence alignments had suggested that the domain contained an integrin metal ion-dependent adhesion site (MIDAS) motif, but the crystal structure shows that the motif is modified and that no metal ion is bound. We have introduced mutations into the vestigial MIDAS motif and report that, unlike the I domain of integrin alpha2beta1, vWF-A3 continues to bind collagen after disruption of the motif. We conclude that collagen recognition by vWF-A3 occurs by a mechanism different from that of the integrin alpha2beta1.
authors.affiliation: Biomedical Engineering Research Center, Boston University, Boston, Massachusetts 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bienkowska
authors.forename: M
authors.initials: M
authors.lastname: Cruz
authors.forename: A
authors.initials: A
authors.lastname: Atiemo
authors.forename: R
authors.initials: R
authors.lastname: Handin
authors.forename: R
authors.initials: R
authors.lastname: Liddington
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003094:Collagen / Q000378:metabolism; D018360:Crystallography, X-Ray; D017931:DNA Primers; D006801:Humans; D046911:Macromolecular Substances; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D055672:Static Electricity; D014841:von Willebrand Factor / Q000737:chemistry* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D046911:Macromolecular Substances; D008670:Metals; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D003094:Collagen