The cysteine-rich region of type VII collagen is a cystine knot with a new topology.

[dystrophic epidermolysis bullosa]

Collagens are a group of extracellular matrix proteins with essential functions for skin integrity . Anchoring fibrils are made of type VII collagen (Col 7 ) and link different skin layers together : the basal lamina and the underlying connective tissue . Col 7 has a central collagenous domain and two noncollagenous domains located at the N and C terminus (NC 1 and NC 2 ), respectively . A cysteine-rich region of hitherto unknown function is located at the transition of the NC 1 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 CX 3 CP . 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 .