1. Copyright © 2016 McGraw-Hill Education. All rights reserved.
From: Epidermolysis Bullosa: The Disease of the Cutaneous Basement Membrane Zone GenBank accession numbers for genes of the cutaneous basement membrane zone (BMZ): LAMA3 (X85108, X85107); LAMC2 (U43327, U311787–U31201); LAMB3 (L25541, U17744–U17760); ITGB4 (X51841, U66529–U66541); ITGA6 (X59512; AF166335–AF166343); COL7A1 (L02870, L23982); PLEC1 (Z54367, U53204, U53834, U63609–U63610); BPAG1 (L11690, M69225); BPAG2 (U76564–U76604); KRT5 (U05838–U05849); KRT5 (NM000526).
The Online Metabolic and Molecular Bases of Inherited Disease, 2014
Legend:
Physiology and pathology of type VII collagen. Synthesis of pro α1(VII) collagen polypeptides and their assembly into anchoring fibrils is depicted at the left side of the figure. The mRNA, ≈9 kb in size, is translated on the ribosomes of cells, such as basal keratinocytes, synthesizing type VII collagen (I). Within the intracellular space (IC) three of these polypeptide chains associate and assemble into a triple-helical type VII collagen molecule, which is then secreted (II and III). In the extracellular space (EC) two triple-helical type VII collagen molecules align into an antiparallel dimer in tail-to-tail orientation with overlapping C-terminal ends (IV). The molecules are processed by proteolytic removal of the NC-2 domains (•), and the association of the dimer is stabilized by disulfide bonding (V). A large number of the dimer molecules laterally assemble in register into anchoring fibrils which contain, at both ends, intact amino-terminal NC1 domains with adhesive properties (VI). In the presence of a mutation in the COL7A1 gene, type VII collagen pathology can manifest as different variants of dystrophic EB. For example, PTCs result in the synthesis of truncated polypeptides unable to form anchoring fibrils, and cause severe Hallopeau-Siemens type of recessive dystrophic EB (HS-RDEB). In the milder, recessively inherited forms of dystrophic EB, known as the Mitis variant (M-RDEB), missense mutations either in a homozygous state or compound heterozygous with a premature termination codon mutation in trans can prevent the assembly of type VII collagen dimers. In case of dominantly inherited dystrophic EB (DDEB), a characteristic mutation is a glycine substitution within the collagenous domain of type VII collagen, which interferes with the packing of the anchoring fibrils and/or compromises the stability of the triple-helical conformation of the type VII collagen molecule. (From Järvikallio et al.36 Used with permission.)
Date of download: 9/18/2016
Copyright © 2016 McGraw-Hill Education. All rights reserved.