Bush Martin, Setiaputra Dheva, Yip Calvin K, Molday Robert S
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
PLoS One. 2016 Jan 26;11(1):e0147653. doi: 10.1371/journal.pone.0147653. eCollection 2016.
RS1, also known as retinoschisin, is a disulphide-linked, discoidin domain containing homo-oligomeric protein that plays a crucial role in maintaining the cellular and synaptic organization of the retina. This is highlighted by the finding that over 130 mutations in RS1 cause X-linked retinoschisis, a retinal degenerative disease characterized by the splitting of the retinal cell layers, disruption of the photoreceptor-bipolar synapses, degeneration of photoreceptors, and severe loss in central vision. In this study, we investigated the arrangement of the RS1 subunits within the oligomer complex using single particle electron microscopy. RS1 was seen as two stacked rings with each ring displaying a symmetrical cog wheel-like structure with eight teeth or projections corresponding to the RS1 subunits. Three dimensional reconstruction and molecular modelling indicated that the discoidin domain, the principal functional unit of RS1, projects outward, and the Rs1 domain and C-terminal segment containing intermolecular disulphide bonds are present in the inner ring to form the core octameric structure. These studies provide a basis for further understanding the role of the novel core RS1 octameric complex in retinal cell biology and X-linked retinoschisis.
RS1，也称为视网膜分裂蛋白，是一种含有同型寡聚体蛋白的二硫键连接的盘状结构域蛋白，在维持视网膜的细胞和突触组织中起关键作用。超过130种RS1突变导致X连锁视网膜劈裂症，这一发现凸显了这一点。X连锁视网膜劈裂症是一种视网膜退行性疾病，其特征是视网膜细胞层分裂、光感受器 - 双极突触破坏、光感受器退化以及中心视力严重丧失。在本研究中，我们使用单颗粒电子显微镜研究了寡聚体复合物中RS1亚基的排列。RS1被视为两个堆叠的环，每个环呈现出对称的齿轮状结构，有八个齿或突起，对应于RS1亚基。三维重建和分子建模表明，RS1的主要功能单元盘状结构域向外突出，而Rs1结构域和含有分子间二硫键的C末端片段存在于内环中，形成核心八聚体结构。这些研究为进一步理解新型核心RS1八聚体复合物在视网膜细胞生物学和X连锁视网膜劈裂症中的作用提供了基础。
