title: The cysteine-rich region of type VII collagen is a cystine knot with a new topology.
abstract: Collagens are a group of extracellular matrix proteins with essential functions for skin integrity. Anchoring fibrils are made of type VII collagen (Col7) and link different skin layers together: the basal lamina and the underlying connective tissue. Col7 has a central collagenous domain and two noncollagenous domains located at the N and C terminus (NC1 and NC2), respectively. A cysteine-rich region of hitherto unknown function is located at the transition of the NC1 domain to the collagenous domain. A synthetic model peptide of this region was investigated by CD and NMR spectroscopy. The peptide folds into a collagen triple helix, and the cysteine residues form disulfide bridges between the different strands. The eight cystine knot topologies that are characterized by exclusively intermolecular disulfide bridges have been analyzed by molecular modeling. Two cystine knots are energetically preferred; however, all eight disulfide bridge arrangements are essentially possible. This novel cystine knot is present in type IX collagen, too. The conserved motif of the cystine knot is CX3CP. The cystine knot is N-terminal to the collagen triple helix in both collagens and therefore probably impedes unfolding of the collagen triple helix from the N terminus.
authors.affiliation: From the Institute of Chemistry and.
authors.forename: Henrik
authors.initials: H
authors.lastname: Wegener
authors.forename: Hauke
authors.initials: H
authors.lastname: Paulsen
authors.forename: Karsten
authors.initials: K
authors.lastname: Seeger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D024081:Collagen Type IX / Q000737:chemistry; D024143:Collagen Type VII / Q000737:chemistry*; D016384:Consensus Sequence; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry*; D047168:Cystine Knot Motifs; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment
chemical_list: D024081:Collagen Type IX; D024143:Collagen Type VII; D004220:Disulfides; D010455:Peptides; D011994:Recombinant Proteins; D003545:Cysteine
keywords: Collagen; Cysteine-mediated Cross-linking; Dystrophic Epidermolysis Bullosa; Extracellular Matrix; Molecular Modeling; NMR; Skin