PROSITE documentation PDOC51403 [for PROSITE entry PS51403]

Collagen IV carboxyl-terminal non-collagenous (NC1) domain profile





Description

Collagens are major components of the extracellular matrices of all metazoan life and play crucial roles in developmental processes and tissue homeostasis. Collagens are composed of three polypeptide chains (α chains) that fold together to form the characteristic triple helical collagenous domain. Some types of triple helical protomers contain genetically identical α chains forming homotrimers, whereas others contain two or three different α chains forming heterotrimers. The sequences required to form a collagenous domain are Gly-X-Y repeats in which the X and Y positions are frequently proline and hydroxyproline. Glycine is required every third residue as it is the only amino acid small enough to pack into the central core of the triple helix. The triple helix-forming parts are surrounded by non-collagenous (NC) domains of variable sequence, size, and shape. Even if the triple helical parts represent the most striking feature of collagens, tissue specificity as well as defined binding of non-collagens seem to be encoded in the NC domains. The terminal NC domains are excised, modified, or incorporated directly into the final suprastructure, depending on protomer type and function [1,2].

Type IV collagen is one of the major constituents of basement membranes, a specialized form of extracellular matrix underlying epithelia that compartmentalizes tissues and provides molecular signals for influencing cell behavior. Each type IV chain contains a long triple-helical collagenous domain flanked by a short 7S domain of 25 residues and a globular non-collagenous NC1 domain of ~230 residues at the N- and C-terminus, respectively. In protomer assembly, the NC1 domains (monomers) of three chains interact, forming an NC1 trimer, to select and register chains for triple helix formation. In network assembly, the NC1 trimers of two protomers interact, forming a NC1 hexamer structure, to select and connect protomers [3,4,5].

The collagen IV NC1 domain contains 12 cysteines, and all of them are involved in disulfide bonds. It folds into a tertiary structure with predominantly β-strands (see <PDB:1LI1; A>). The collagen IV MC1 domain is composed of two similarly folded subdomains stabilized by 6 intrachain disulfide bonds involving the following pairs: C1-C6, C2-C5, C3-C4, C7-C12, C8-C11, and C9-C10. Each subdomain represents a compact disulfide-stabilized triangular structure, from which a finger-like hairpin loop projects into an incompletely formed six-stranded β-sheet of an adjacent subdomain of the same or of an adjacent chain clamping the subdomains tightly together [3,4,5].

The profile we developed covers the entire collagen IV NC1 domain.

Last update:

November 2011 / First entry.

Technical section

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

NC1_IV, PS51403; Collagen IV carboxyl-terminal non-collagenous (NC1) domain profile  (MATRIX)


References

1AuthorsBoot-Handford R.P., Tuckwell D.S.
TitleFibrillar collagen: the key to vertebrate evolution? A tale of molecular incest.
SourceBioessays 25:142-151(2003).
PubMed ID12539240
DOI10.1002/bies.10230

2AuthorsBork P.
TitleThe modular architecture of vertebrate collagens.
SourceFEBS Lett. 307:49-54(1992).
PubMed ID1639194

3AuthorsThan M.E., Henrich S., Huber R., Ries A., Mann K., Kuehn K., Timpl R., Bourenkov G.P., Bartunik H.D., Bode W.
TitleThe 1.9-A crystal structure of the noncollagenous (NC1) domain of human placenta collagen IV shows stabilization via a novel type of covalent Met-Lys cross-link.
SourceProc. Natl. Acad. Sci. U.S.A. 99:6607-6612(2002).
PubMed ID12011424
DOI10.1073/pnas.062183499

4AuthorsSundaramoorthy M., Meiyappan M., Todd P., Hudson B.G.
TitleCrystal structure of NC1 domains. Structural basis for type IV collagen assembly in basement membranes.
SourceJ. Biol. Chem. 277:31142-31153(2002).
PubMed ID11970952
DOI10.1074/jbc.M201740200

5AuthorsVanacore R.M., Shanmugasundararaj S., Friedman D.B., Bondar O., Hudson B.G., Sundaramoorthy M.
TitleThe alpha1.alpha2 network of collagen IV. Reinforced stabilization of the noncollagenous domain-1 by noncovalent forces and the absence of Met-Lys cross-links.
SourceJ. Biol. Chem. 279:44723-44730(2004).
PubMed ID15299013
DOI10.1074/jbc.M406344200



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)