The von Willebrand factor is a large multimeric glycoprotein found in bloodplasma. Mutant forms are involved in the aetiology of bleeding disorders [<cite idref="PUB00001522"/>]. In von Willebrand factor, the type A domain (vWF) is the prototype fora protein superfamily. The vWF domain is found in various plasma proteins:complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins [<cite idref="PUB00003554"/>, <cite idref="PUB00003322"/>, <cite idref="PUB00001619"/>]. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteinsthat incorporate vWF domains participate in numerous biological events(e.g. cell adhesion, migration, homing, pattern formation, and signaltransduction), involving interaction with a large array of ligands [<cite idref="PUB00003554"/>]. A number of human diseases arise from mutations in VWA domains. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of alpha-helices and beta-strands [<cite idref="PUB00003322"/>]. Foldrecognition algorithms were used to score sequence compatibility with alibrary of known structures: the vWF domain fold was predicted to be adoubly-wound, open, twisted beta-sheet flanked by alpha-helices [<cite idref="PUB00001681"/>]. 3D structures have been determined for the I-domains of integrins CD11b(with bound magnesium) [<cite idref="PUB00000913"/>] and CD11a (with bound manganese) [<cite idref="PUB00004855"/>]. The domain adopts a classic alpha/beta Rossmann fold and contains an unusual metal ion coordination site at its surface. It has been suggested that this siterepresents a general metal ion-dependent adhesion site (MIDAS) for binding protein ligands [<cite idref="PUB00000913"/>]. The residues constituting the MIDAS motif in the CD11band CD11a I-domains are completely conserved, but the manner in which the metal ion is coordinated differs slightly [<cite idref="PUB00004855"/>].