Protomers create basement-membrane networks with other protomers by uniting two NC1 trimers to form an interface hexamer at the C-terminal and by uniting four triple helical 7S domains at the N-terminal (panel A). A network composed of alpha 3, 4, 5 (type IV) protomers is illustrated, showing end-to-end connections of individual protomer units, supercoiling and looping of the triple helixes, and disulfide cross-links between triple helical domains.[1-4] The structure of the NC1 hexamer is determined by the particular alpha chains that form a triple helical protomer and by the particular canonical protomers that can connect to adjoining protomers (NC1 box). Molecular recognition sequences encoded within NC1 domains govern the selection of partner chains for both protomer and network assembly. The 7S domains also play a key part in determining the specificity, affinity, and geometry of the tetramer formed through the connection of four protomers (7S box).[4-6] Two other networks are composed of pairs of alpha 1, 1, 2(IV) hexamers or alpha 1, 1, 2(IV)–alpha 5, 5, 6(IV) NC1 hexamers.[1-4] The alpha 3, 4, 5 (IV)–alpha 3, 4, 5(IV) network differs from the others in that it has a greater number of disulfide cross-links between triple helical domains, which increases its resistance to proteolysis.[7]
Panel B shows the three-dimensional model of the alpha 3, 4, 5(IV) NC1 hexamer that is depicted in the NC1 box in panel A. The three-dimensional structure and the location of epitopes were determined by computer modeling of the crystal structure of the alpha 1, 1, 2(IV)–alpha 1, 1, 2(IV) hexamer[8] and the apparent quaternary structure of the alpha 3, 4, 5(IV) hexamer.[2] The hexamer is composed of two trimeric caps, each derived from adjacent protomers. Each trimer consists of an alpha 3 monomer (red), an alpha 4 monomer (blue), and an alpha 5 monomer (green). The monomers have a novel tertiary structure with two homologous subdomains, each of which is characterized by beta-sheet motifs. The model depicts the location of the EA (yellow) and EB (gold) regions that encompass two dominant epitopes for Goodpasture antibodies. The epitopes reside in the alpha 3(IV) NC1 domain, near the triple helical junction, and they are partially sequestered by interactions with the alpha 5(IV) and alpha 4(IV) NC1 domains, respectively.From: Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med 2003; 348:2543. Copyright © 2003 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Do you want to add Medilib to your home screen?