Molecular cloning and characterization of type VII collagen cDNA

doi:10.1016/S0006-291X(05)80283-9

Biochemical and Biophysical Research Communications

Volume 183, Issue 3, 31 March 1992, Pages 958-963

https://doi.org/10.1016/S0006-291X(05)80283-9 Get rights and content

Summary

Type VII collagen, located in human epidermal basement membrane, is the primary pathogenic target molecule in epidermolysis bullosa acquisita and epidermolysis bullosa dystrophica. Using a monoclonal antibody against the non-collagenous domain of type VII collagen, ∼ 1Kb cDNA was isolated from human keratinocyte library. The deduced primary structure of this clone thus reflects the non-collagenous domain of type VII collagen that may be involved in cell attachment. This region shows a weak homology (∼23%) to the cell attachment domain of fibronectin. Northern blot revealed ∼9.5 Kb single band.

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Cited by (15)

Bullous systemic lupus erythematosus: Detection of antibodies against noncollagenous domain of type VII collagen
1998, Journal of the American Academy of Dermatology
A 9-year-old girl with systemic lupus erythematosus developed bullous eruption. Histopathologic examination showed subepidermal blistering and immunoglobulins (IgG, IgM, IgA) and complement components (C1q, C3) deposited linearly at the basement membrane zone. IgG in this patient’s serum bound to the dermal side of 1 mol/L sodium chloride-split normal human skin, and a 290 kd protein was identified in the dermal extract. The patient’s serum recognized various epitopes on the noncollagenous domain as demonstrated by the use of fusion proteins of type VII collagen. Resolution of the bullous eruption occurred after treatment with dapsone. (J Am Acad Dermatol 1998;38:844-8.)
Immunodominant autoepitopes of type VII collagen are short, paired peptide sequences within the fibronectin type III homology region of the noncollagenous (NC1) domain
1995, Journal of Investigative Dermatology
Autoantibodies to type VII collagen are associated with the blistering diseases epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. We showed previously that these autoantibodies recognize epitopes within the noncollagenous (NC1) region of type VII collagen. That region is composed of fibronectin type III homology units that may contribute to intermolecular cross-linking and basement membrane adhesion functions of type VII collagen. In this study, we defined the specific amino acid sequences recognized by these autoantibodies. By fusion protein analysis, sera from patients with epidermolysis bullosa acquisita and bullous lupus were found to react with two regions within the fourth (E-1) and eighth (E-2) fibronectin homology repeats, each consisting of approximately 100 amino acids, Affinity purification studies showed E-1 and E-2 to be independent and non-cross-reactive epitope regions. These regions were probed further by enzyme-linked immunosorbent assay analysis of overlapping octapeptide sets derived from the amino acid sequences of E-1 and E-2. The results showed two reactive, closely associated octapeptide sequences within each region, both lying in amphipathic portions of fibronectin type III homology repeats These studies identify short peptide sequences within the NC1 domain of type VII collagen that are targeted independently by autoantibodies. These sequences may play a direct role in determining the properties of type VII collagen that influence adhesion between this molecule and other basement membrane proteins, and their alteration by antibody binding may be the immunopathogenic event underlying epidermolysis bullosa acquisita and bullous lupus.
Epitope mapping for epidermolysis bullosa acquisita autoantibody by molecularly cloned cDNA for type VII collagen
1994, Journal of Investigative Dermatology
Epidermolysis bullosa acquisita is a subepidermal blistering disease in which patients have autoantibodies against the non-collagenous domain of type VII collagen. Starting with previously isolated 1-kilobase pair (Kb) cDNA for this au- toantigen, we isolated overlapping cDNAs with a combined open reading frame of -&∼3.2 Kb, encoding most (&∼115 kilo- daltons [KDa]) of the N-terminal non-collagenous domain of type VII collagen. To localize immunogenic domains, we produced maltose-binding fusion proteins with cDNA encoding different portions of this autoantigen. These cDNA fragments scan from 5' to 3' of this non-collagenous domain and overlap each other. An immunoblot analysis of these fusion proteins with eight epidermolysis bullosa acquisita patient sera demonstrated that each patient serum binds to different regions of this molecule and that epitopes for these patient sera locate throughout this autoantigen. These data suggest that multiple epitopes on the N-terminal non-collagenous domain of type VII collagen are recognized by circulating autoantibodies in patients with epidermolysis bullosa acquisita.
Collagen Genes: Mutations Affecting Collagen Structure and Expression
1994, Progress in Nucleic Acid Research and Molecular Biology
This chapter discusses the collagen genes in which naturally occurring or induced mutations have been characterized. It includes the genes that encode collagens types I, II, III, IV, VII, IX, and X. The collagens are a complex family of secreted molecules that share similar triple-helical motifs and have a structural role in the extracellular matrix. There are at least 26 different collagen polypeptide chains encoded by 26 unique collagen genes. Roman numerals are used to identify each of the collagens, and Arabic numerals represent individual polypeptide chains, referred to as α-chains. The gene symbols indicate the type of collagen and α -chain. For example, in the symbol COL1A1, COL1 indicates type-I collagen and A1 indicates the α-l chain of this collagen. The collagens can be grouped into categories according to their α-chain characteristics, molecular assembly, and supramolecular structures. The most widespread and abundant collagens are the fibrillar collagens, types I, II, III, V, and XI. Descriptions of other collagen genes and the genes that encode the post-translational modifying enzymes are described in the chapter.
Type VII collagen, anchoring fibrils, and epidermolysis bullosa
1993, Journal of Investigative Dermatology
The anchoring fibrils at the dermal-epidermal junction have been well characterized as ultrastructural entities. From their appearance, it was proposed that they fortified the attachment of the epidermis to the dermis. This hypothesized function was strengthened by observations indicating that the anchoring fibrils were abnormal, diminished, or absent from individuals with dystrophic epidermolysis bullosa. Therefore, characterization of the molecular constituents of the anchoring fibrils and their interactions with other basement membrane and dermal components might lead to identification of the gene defects underlying at least some forms of epidermolysis bullosa. Type VII collagen was identified as the protein component of anchoring fibrils in 1986. Since then, the major characteristics of the molecule have been described. These are consistent with a model wherein secreted type VII collagen molecules form disulfide-bond stabilized antiparallel dimers. The dimers then condense laterally into unstaggered arrays that are the anchoring fibrils. This arrangement allows for the protrusion of large globular domains (NC-1) from both ends of the fibrils. The aggregated triple-helical domains extend into the papillary dermis and entrap fibrous dermal components. The NC-1 domains are believed to interact with components of the basement membrane and thus to mediate the attachment of the basement membrane to the dermis. This model predicts that mutations in the type VII collagen gene that prevent the secretion of the molecule will be the most devastating, whereas mutations in the regions encoding the globular domains may show more variable phenotype. Ultimately, understanding the function of type VII collagen at the molecular level will be the key to devising strategies to moderate the pathophysiology of dystrophic epidermolysis bullosa.
Type VII and XVII collagen mRNA expressions in regenerated epidermal laminae in chronic equine laminitis
2008, Journal of Equine Science

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Molecular cloning and characterization of type VII collagen cDNA

Summary

J. Biol. Chem.

J. Invest. Dermatol.

J. Biol. Chem.

J. Biol. Chem.

J. Cell. Biol.

J. Biol. Chem.