Collagen IV Exploits a Cl- Step Gradient for Scaffold Assembly

Collagen IV of basement membranes: IV. Adaptive mechanism of collagen IV scaffold assembly in Drosophila

“…Analogously to human crystal structures of α112 and α345 NC1 hexamers ( 28 , 29 , 53 ), we found multiple PEG molecules associated on the surface and in the inner cavity of the Drosophila NC1 hexamer ( Fig. S24 ).…”

“…Out of 12 chloride ions found at the hexamer interface in mammals ( 28 , 29 , 53 , 57 ) only four were found in Drosophila ( Fig. 10 A and Table S4 ).…”

“…In mammals, the NC1 hexamer assembly is triggered by a high concentration of extracellular chloride ions outside the cell ( 26 , 27 ). Namely, 12 Cl - ions are involved in the assembly and stabilization of the NC1 hexamer, forming a ring at the interface between two protomers ( 28 , 29 ). The chloride-dependent mechanism evolved early in cnidarians and has been preserved up to mammals ( 28 , 30 ).…”

Lysyl hydroxylase 3–mediated post-translational modifications are required for proper biosynthesis of collagen α1α1α2(IV)

“…To better characterize collagen α1α1α2(IV) oligomeric structures and network formation, we performed rotary shadow electron microscopy on samples isolated from WT and LH3 KO PFHR9 cells. During type IV collagen network formation, two collagen α1α1α2(IV) heterotrimers associate with each other by way of head-to-head interactions of their carboxy terminal NC1 domains (hexamers) ( 61 ) and four collagen α1α1α2(IV) heterotrimers interact by way of lateral and antiparallel interactions of their amino-terminal 7S domains (dodecamers) ( 62 ). Electron micrographs from WT PFHR9 cells showed that over 80% of the collagen α1α1α2(IV) was trimeric, but we also found frequent examples of hexamers (∼8.5%) and dodecamers (∼9.0%; Fig.…”

Prospective collagen IVα345 therapies for Alport syndrome

“…The hexamer structure (Fig. 2b) revealed a ring of twelve chloride ions at the trimer-trimer interface, analogous to the collagen IV α121 scaffold [20 ▪▪ ,22 ▪▪ ]. The surface of the α345 hexamer is marked by multiple pores and crevices that are potentially accessible to small molecules.…”