Department of Medicine, Division of Nephrology.
Center for Structural Biology.
Curr Opin Nephrol Hypertens. 2018 May;27(3):171-175. doi: 10.1097/MNH.0000000000000401.
The purpose of this review is to highlight recent advances in understanding the molecular assembly of basement membranes, as exemplified by the glomerular basement membrane (GBM) of the kidney filtration apparatus. In particular, an essential role of halogens in the basement membrane formation has been discovered.
Extracellular chloride triggers a molecular switch within non collagenous domains of collagen IV that induces protomer oligomerization and scaffold assembly outside the cell. Moreover, bromide is an essential cofactor in enzymatic cross-linking that reinforces the stability of scaffolds. Halogenation and halogen-induced oxidation of the collagen IV scaffold in disease states damage scaffold function.
Halogens play an essential role in the formation of collagen IV scaffolds of basement membranes. Pathogenic damage of these scaffolds by halogenation and halogen-induced oxidation is a potential target for therapeutic interventions.
本文旨在强调对基底膜分子组装的最新认识进展,以肾脏滤过装置的肾小球基底膜(GBM)为例。特别是,卤族元素在基底膜形成中的重要作用已经被发现。
细胞外的氯离子在 IV 型胶原的非胶原结构域内触发分子开关,诱导原聚体寡聚化,并在细胞外组装支架。此外,溴化物是酶交联的必需辅因子,可增强支架的稳定性。在疾病状态下,卤化和卤化物诱导的 IV 型胶原支架氧化会破坏支架功能。
卤族元素在基底膜胶原 IV 支架的形成中起着至关重要的作用。通过卤化和卤化物诱导的氧化对这些支架的致病损伤是治疗干预的潜在靶点。