Chain composition of type IV collagen networks in basement membranes

被引:0
|
作者
Noelken, ME [1 ]
Hudson, BG [1 ]
机构
[1] Univ Kansas, Ctr Med, Dept Biochem & Mol Biol, Kansas City, KS 66169 USA
关键词
type IV collagen; basement membrane; Alport syndrome; glomerulus; seminiferous tubule;
D O I
暂无
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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(NC1) 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 NC1 hexamers excised by collagenase digestion. Three major hexamer populations were obtained that contained al(IV) and alpha 2(IV) chains, alpha l(IV)-alpha 6(IV) chains, and alpha 3(IV)-alpha 6(IV) chains, respectively, which indicated three major separate type IV collagen networks in STEM. 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, and alpha 1(IV) through alpha 5(IV) chains cross-linked between NCl domains as well between triple helices. The latter set of fragments contained a subset of disulfide-linked alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains. The existence of networks containing alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains suggests a molecular basis for mutations in the gene encoding the aS(IV) chain causing defective assembly of not only alpha 5(IV) chains, but also alpha 3(IV) and alpha 4(IV) chains in the GBM of patients with Alport syndrome. A significant result of these studies is that GEM contains three major type IV collagen networks: alpha 1(IV).alpha 2(IV), alpha 1(IV)-alpha 5(IV) and alpha 3(IV) . alpha 4(IV) . alpha 5(IV), similar to those of STBM, which also contains alpha 6(IV) chains in the latter two networks.
引用
收藏
页码:159 / 169
页数:11
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