Collagen IV^α345 dysfunction in glomerular basement membrane diseases. II. Crystal structure of the α345 hexamer.

ABSTRACT: 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. The α345 hexamer structure revealed a ring of 12 chloride ions at the trimer-trimer interface, analogous to the collagen α121 hexamer, and the location of the 170 AS variants. The hexamer surface is marked by multiple pores and crevices that are potentially accessible to small molecules. Loo

SUBMITTER: Boudko SP 

PROVIDER: S-EPMC8093946 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature