Glycobiology and Extracellular Matrices
Collagen IVα345 dysfunction in glomerular basement membrane diseases. II. Crystal structure of the α345 hexamer
Our recent work identified a genetic variant of the α345 hexamer of the collagen IV scaffold that is present in patients with glomerular basement membrane diseases, Goodpasture’s disease (GP) and Alport syndrome (AS), and phenocopies of AS in knock-in mice. To understand the context of this “Zurich” variant, an 8-amino acid appendage, we developed a construct of the WT α345 hexamer using the single-chain NC1 trimer technology, which allowed us to solve a crystal structure of this key connection module.Collagen IVα345 dysfunction in glomerular basement membrane diseases. III. A functional framework for α345 hexamer assembly
We identified a genetic variant, an 8-residue appendage, of the α345 hexamer of collagen IV present in patients with glomerular basement membrane diseases, Goodpasture’s disease and Alport syndrome, and determined the long-awaited crystal structure of the hexamer. We sought to elucidate how variants cause glomerular basement membrane disease by exploring the mechanism of the hexamer assembly. Chloride ions induced in vitro hexamer assembly in a composition-specific manner in the presence of equimolar concentrations of α3, α4, and α5 NC1 monomers.
