title: Noncollagenous (NC1) domain of collagen VII resembles multidomain adhesion proteins involved in tissue-specific organization of extracellular matrix.
abstract: Type VII collagen (C7) is a stratified squamous epithelial basement membrane protein composed of three identical alpha chains, each consisting of a 145-kDa amino-terminal noncollagenous (NC1) domain and a 145-kDa carboxyl-terminal collagenous domain. Morphologic and biochemical studies have shown that tissue-specific aggregates of C7 dimers called anchoring fibrils may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen. In this study, we cloned a cDNA encoding most of the NC1 domain of C7. The deduced amino acid sequence revealed motifs characteristic of multidomain ECM proteins that contribute to the tissue-specific organization of ECM including a region of 7 1/2 sequential fibronectin type III (Fn III) homology repeats, a potential collagen-binding region homologous to the A domain of von Willebrand factor (vWf) and an RGD sequence. A purified C7 fusion protein containing these motifs specifically bound to type IV collagen in a functional assay. These results suggest that regions within the NC1 domain of C7 mediate interactions with lamina densa and dermal ECM proteins including type IV collagen. Structural mutations and autoepitopes in these regions may represent mechanisms for the development of defective basement membrane organization and adherence in genetic and autoimmune forms of epidermolysis bullosa.
authors: Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill.
authors: W R
authors: WR
authors: Gammon
authors: M L
authors: ML
authors: Abernethy
authors: K M
authors: KM
authors: Padilla
authors: P S
authors: PS
authors: Prisayanh
authors: M E
authors: ME
authors: Cook
authors: J
authors: J
authors: Wright
authors: R A
authors: RA
authors: Briggaman
authors: S W
authors: SW
authors: Hunt
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003094:Collagen / Q000737:chemistry*; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D015815:Cell Adhesion Molecules; D011993:Recombinant Fusion Proteins; D003094:Collagen