G2FG2 nidogen domain and fibulin
|SMART accession number:||SM00682|
|Interpro abstract (IPR006605):|
Basement membranes are sheet-like extracellular matrices found at the basal surfaces of epithelia and condensed mesenchyma. By preventing cell mixing and providing a cell-adhesive substrate, they play crucial roles in tissue development and function. Basement menbranes are composed of an evolutionarily ancient set of large glycoproteins, which includes members of the laminin family, collagen IV, perlecan and nidogen/entactin. Nidogen/entactin is an important basement membrane component, which promotes cell attachment, neutrophil chemotaxis, trophoblast outgrowth, and angiogenesis. It consists of three globular regions, G1-G3. G1 and G2 are connected by a thread-like structure, whereas that between G2 and G3 is rod-like [(PUBMED:9633511), (PUBMED:11427896)].
The nidogen G2 region binds to collagen IV and perlecan. The nidogen G2 structure is composed of two domains, an N-terminal EGF-like domain and a much larger beta-barrel domain of ~230 residues. The nidogen G2 beta-barrel consists of an 11-stranded beta-barrel of complex topology, the interior of which is traversed by the hydrophobic, predominantly alpha helical segment connecting strands C and D. The N-terminal half of the barrel comprises two beta-meanders (strands A-C and D-F) linked by the buried alpha-helical segment. The polypeptide chain then crosses the bottom of the barrel and forms a five-stranded Greek key motif in the C- terminal half of the domain. Helix alpha3 caps the top of the barrel and forms the interface to the EGF-like domain. The nidogen G2 beta-barrel domain has unexpected structural similarity to green fluorescent protein, suggesting that they derive from a common ancestor. A large surface patch on the barrel surface is strikingly conserved in all metazoan nidogens. Site-directed mutagenesis demonstrates that the conserved residues in the conserved patch are involved in the binding of perlecan, and possibly also of collagen IV [(PUBMED:11427896)].
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