title: Supramolecular interactions in the dermo-epidermal junction zone: anchoring fibril-collagen VII tightly binds to banded collagen fibrils.
abstract: The dermis and the epidermis of normal human skin are functionally separated by a basement membrane but, together, form a stable structural continuum. Anchoring fibrils reinforce this connection by insertion into the basement membrane and by intercalation with banded collagen fibrils of the papillary dermis. Structural abnormalities in collagen VII, the major molecular constituent of anchoring fibrils, lead to a congenital skin fragility condition, dystrophic epidermolysis bullosa, associated with skin blistering. Here, we characterized the molecular basis of the interactions between anchoring fibrils and banded collagen fibrils. Suprastructural fragments of the dermo-epidermal junction zone were generated by mechanical disruption and by separation with magnetic Immunobeads. Anchoring fibrils were tightly attached to banded collagen fibrils. In vitro binding studies demonstrated that a von Willebrand factor A-like motif in collagen VII was essential for binding of anchoring fibrils to reconstituted collagen I fibrils. Since collagen I and VII molecules reportedly undergo only weak interactions, the attachment of anchoring fibrils to collagen fibrils depends on supramolecular organization of their constituents. This complex is stabilized in situ and resists dissociation by strong denaturants.
authors.affiliation: Institute for Physiological Chemistry and Pathobiochemistry, University Hospital of Münster, 48149 Münster, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Villone
authors.forename: Anja
authors.initials: A
authors.lastname: Fritsch
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
authors.forename: Peter
authors.initials: P
authors.lastname: Bruckner
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D024042:Collagen Type I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024143:Collagen Type VII / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000737:chemistry* / Q000378:metabolism; D004817:Epidermis / Q000737:chemistry* / Q000378:metabolism; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D011485:Protein Binding / Q000235:genetics
chemical_list: D024042:Collagen Type I; D024143:Collagen Type VII; D046912:Multiprotein Complexes