View source for 5nb2


==Crystal structures of homooligomers of collagen type IV. alpha2NC1==
<StructureSection load='5nb2' size='340' side='right'caption='[[5nb2]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nb2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NB2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5nb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nb2 OCA], [https://pdbe.org/5nb2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nb2 RCSB], [https://www.ebi.ac.uk/pdbsum/5nb2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nb2 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CO4A2_HUMAN CO4A2_HUMAN] Defects in COL4A2 are the cause of porencephaly type 2 (POREN2) [MIM:[https://omim.org/entry/614483 614483]. POREN2 is a neurologic disorder characterized by a fluid-filled cysts or cavities within the cerebral hemispheres. Affected individuals typically have hemiplegia, seizures, and intellectual disability. Porencephaly type 2, or schizencephalic porencephaly, is usually symmetric and represents a primary defect in the development of the cerebral ventricles.<ref>PMID:22209246</ref>   Defects in COL4A2 are a cause of susceptibility to intracerebral hemorrhage (ICH) [MIM:[https://omim.org/entry/614519 614519]. ICH is a pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.<ref>PMID:22209247</ref> 
== Function ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nb2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Collagen 3D structures|Collagen 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Casino P]]
[[Category: Marina A]]