• Chain composition of type IV collagen networks in basement membranes

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    • Keywords


      Type IV collagen; basement membrane; Alport syndrome; glomerulus, seminiferous tubule

    • Abstract


      Type IV collagen, the major component of basement membranes (BM), is a family of six very similar chains. This allows for many kinds (isoforms) of triple helical protomers. The protomers self-assemble into network-like supramolecular structures by dimerization through C-terminal (NCl) domains (resulting in six chains forming an NC1 hexamer), and tetramerization through the protomer N-terminal domain. Studies on the networks of seminiferous tubule BM (STBM) involved affinity chromatography to fractionate NCl hexamers excised by collagenase digestion. Three major hexamer populations were obtained that containedα1(IV) andα2(IV) chains,α1(IV)-α6(IV) chains, andα3(IV)-α6(IV) chains, respectively, which indicated three major separate type IV collagen networks in STBM. To study glomerular BM, we used selective proteolysis to separate large fragments of type IV collagen. These contained type IV collagen chains cross-linked between NCl domains, andα1(IV) throughα5(IV) chains cross-linked between NC1 domains as well between triple helices. The latter set of fragments contained a subset of disulfidelinkedα3(IV),α4(IV) andα5(IV) chains. The existence of networks containingα3(IV),α4(IV) andα5(IV) chains suggests a molecular basis for mutations in the gene encoding theα5(IV) chain causing defective assembly of not onlyα5(IV) chains, but alsoα3(IV) andα4(IV) chains in the GBM of patients with Alport syndrome. A significant result of these studies is that GBM contains three major type IV collagen networks:α1(IV) ·α2(IV),α1(IV)-α5(IV) andα3(IV) ·α4(IV) ·α5(IV), similar to those of STBM, which also containsα6(IV) chains in the latter two networks.

    • Author Affiliations


      Milton E Noelken1 Billy G Hudson1

      1. Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas - 66169-7421, USA
    • Dates

  • Journal of Chemical Sciences | News

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