Building collagen IV smart scaffolds on the outside of cells

• Published in: Protein science Vol. 26; no. 11; pp. 2151 - 2161
• Main Authors: Brown, Kyle L., Cummings, Christopher F., Vanacore, Roberto M., Hudson, Billy G.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-11-2017; John Wiley and Sons Inc
• Subjects: Amino Acid Motifs; Amino Acid Oxidoreductases - genetics; Amino Acid Oxidoreductases - metabolism; Animals; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; basement membrane; Basement Membrane - metabolism; Basement Membrane - ultrastructure; Binding sites; chloride; Collagen; Collagen (type IV); collagen IV; Collagen Type IV - chemistry; Collagen Type IV - genetics; Collagen Type IV - metabolism; Cross-linking; Crosslinking; Eukaryotic Cells - metabolism; Eukaryotic Cells - ultrastructure; extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix - ultrastructure; Gene Expression Regulation; Humans; Molecular modelling; Networks; Oligomerization; Peroxidases; Protein Interaction Domains and Motifs; Protein Multimerization; Protein Structure, Secondary; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - metabolism; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - metabolism; Review; Reviews; scaffold; Scaffolds; Tissues; chloride; collagen IV; basement membrane; scaffold; extracellular matrix
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.3283

Collagen IV scaffolds assemble through an intricate pathway that begins intracellularly and is completed extracellularly. Multiple intracellular enzymes act in concert to assemble collagen IV protomers, the building blocks of collagen IV scaffolds. After being secreted from cells, protomers are activated to initiate oligomerization, forming insoluble networks that are structurally reinforced with covalent crosslinks. Within these networks, embedded binding sites along the length of the protomer lead to the “decoration” of collagen IV triple helix with numerous functional molecules. We refer to these networks as “smart” scaffolds, which as a component of the basement membrane enable the development and function of multicellular tissues in all animal phyla. In this review, we present key molecular mechanisms that drive the assembly of collagen IV smart scaffolds.