5nax

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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CO4A1_HUMAN CO4A1_HUMAN]] Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.<ref>PMID:10811134</ref> <ref>PMID:16481288</ref> <ref>PMID:16151532</ref> <ref>PMID:18775695</ref> Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation. Inhibits expression of hypoxia-inducible factor 1alpha and ERK1/2 and p38 MAPK activation. Ligand for alpha1/beta1 integrin.<ref>PMID:10811134</ref> <ref>PMID:16481288</ref> <ref>PMID:16151532</ref> <ref>PMID:18775695</ref> [[http://www.uniprot.org/uniprot/CO4A2_HUMAN CO4A2_HUMAN]] Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.<ref>PMID:10625665</ref> <ref>PMID:12876280</ref> <ref>PMID:15899827</ref> Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins.<ref>PMID:10625665</ref> <ref>PMID:12876280</ref> <ref>PMID:15899827</ref>
[[http://www.uniprot.org/uniprot/CO4A1_HUMAN CO4A1_HUMAN]] Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.<ref>PMID:10811134</ref> <ref>PMID:16481288</ref> <ref>PMID:16151532</ref> <ref>PMID:18775695</ref> Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation. Inhibits expression of hypoxia-inducible factor 1alpha and ERK1/2 and p38 MAPK activation. Ligand for alpha1/beta1 integrin.<ref>PMID:10811134</ref> <ref>PMID:16481288</ref> <ref>PMID:16151532</ref> <ref>PMID:18775695</ref> [[http://www.uniprot.org/uniprot/CO4A2_HUMAN CO4A2_HUMAN]] Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.<ref>PMID:10625665</ref> <ref>PMID:12876280</ref> <ref>PMID:15899827</ref> Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins.<ref>PMID:10625665</ref> <ref>PMID:12876280</ref> <ref>PMID:15899827</ref>
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== Publication Abstract from PubMed ==
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Basement membranes are extracellular structures of epithelia and endothelia that have collagen IV scaffolds of triple alpha-chain helical protomers that associate end-to-end, forming networks. The molecular mechanisms by which the noncollagenous C-terminal domains of alpha-chains direct the selection and assembly of the alpha1alpha2alpha1 and alpha3alpha4alpha5 hetero-oligomers found in vivo remain obscure. Autoantibodies against the noncollagenous domains of the alpha3alpha4alpha5 hexamer or mutations therein cause Goodpasture's or Alport's syndromes, respectively. To gain further insight into oligomer-assembly mechanisms as well as into Goodpasture's and Alport's syndromes, crystal structures of non-collagenous domains produced by recombinant methods were determined. The spontaneous formation of canonical homohexamers (dimers of trimers) of these domains of the alpha1, alpha3 and alpha5 chains was shown and the components of the Goodpasture's disease epitopes were viewed. Crystal structures of the alpha2 and alpha4 non-collagenous domains generated by recombinant methods were also determined. These domains spontaneously form homo-oligomers that deviate from the canonical architectures since they have a higher number of subunits (dimers of tetramers and of hexamers, respectively). Six flexible structural motifs largely explain the architectural variations. These findings provide insight into noncollagenous domain folding, while supporting the in vivo operation of extrinsic mechanisms for restricting the self-assembly of noncollagenous domains. Intriguingly, Alport's syndrome missense mutations concentrate within the core that nucleates the folding of the noncollagenous domain, suggesting that this syndrome, when owing to missense changes, is a folding disorder that is potentially amenable to pharmacochaperone therapy.
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Structures of collagen IV globular domains: insight into associated pathologies, folding and network assembly.,Casino P, Gozalbo-Rovira R, Rodriguez-Diaz J, Banerjee S, Boutaud A, Rubio V, Hudson BG, Saus J, Cervera J, Marina A IUCrJ. 2018 Oct 10;5(Pt 6):765-779. doi: 10.1107/S2052252518012459. eCollection, 2018 Nov 1. PMID:30443360<ref>PMID:30443360</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5nax" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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<references/>

Revision as of 20:43, 2 December 2018

Crystal structures of homooligomers of the non-collagenous domains of collagen type IV. alpha121NC1

5nax, resolution 2.82Å

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