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PROSITE documentation PDOC50993
Nidogen G2 beta-barrel domain profile


Description

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 [1,2].

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 (see <PDOC00021>) and a much larger β-barrel domain of ~230 residues (see <PDB:1H4U>). The nidogen G2 β-barrel consists of an 11-stranded β-barrel of complex topology, the interior of which is traversed by the hydrophobic, predominantly α helical segment connecting strands C and D. The N-terminal half of the barrel comprises two β-meanders (strands A-C and D-F) linked by the buried α-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 α3 caps the top of the barrel and forms the interface to the EGF-like domain. The nidogen G2 β-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 [2].

The profile we developed covers the entire nidogen G2 β-barrel domain.

Last update:

May 2004 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

NIDOGEN_G2, PS50993; Nidogen G2 beta-barrel domain profile  (MATRIX)


References

1AuthorsKimura N. Toyoshima T. Kojima T. Shimane M.
TitleEntactin-2: a new member of basement membrane protein with high homology to entactin/nidogen.
SourceExp. Cell Res. 241:36-45(1998).
PubMed ID9633511

2AuthorsHopf M. Goehring W. Ries A. Timpl R. Hohenester E.
SourceNat. Strum. Biol. 8:634-640(2001).



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