title: The vWFA2 domain of type VII collagen is responsible for collagen binding.
abstract: Type VII collagen (Col7) is the major component of anchoring fibrils and very important for skin integrity. This is emphasized by the Col7 related skin blistering diseases dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita. Structural data that provides insights into the interaction network of Col7 and thus providing a basis for a better understanding of the pathogenesis of the diseases is missing. We proved that the von-Willebrand-factor A like domain 2 (vWFA2) of Col7 is responsible for type I collagen binding. The interaction has a K(D) value of 90 μM as determined by SPR and is enthalpy driven as derived from the van't Hoff equation. Furthermore, a hitherto unknown interaction of this domain with type IV collagen was identified. The interaction of vWFA2 with type I collagen is sensitive to the presence of magnesium ions, however, vWFA2 does not contain a magnesium binding site thus magnesium must bind to type I collagen. A lysine residue has been identified to be crucial for type I collagen binding. This allowed localization of the binding site. Mutational analysis suggests different interaction mechanisms in different species and that these interactions might be of covalent nature.
authors.affiliation: Institute of Chemistry, University of Lübeck, 23538 Lübeck, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Wegener
authors.forename: Sarah
authors.initials: S
authors.lastname: Leineweber
authors.forename: Karsten
authors.initials: K
authors.lastname: Seeger
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D024042:Collagen Type I / Q000378:metabolism*; D024143:Collagen Type VII / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D024042:Collagen Type I; D024143:Collagen Type VII; D014841:von Willebrand Factor; D008274:Magnesium; D008239:Lysine