Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA.
Faculty of Chemistry, Technische Universität Dresden, Dresden, Germany.
Adv Exp Med Biol. 2023;1415:499-505. doi: 10.1007/978-3-031-27681-1_73.
Rods and cones are photoreceptor neurons in the retina that are required for visual sensation in vertebrates, where proper protein localization and compartmentalization are critical for phototransduction and visual function. In human retinal diseases, improper protein transport to the outer segment (OS) or mislocalization of proteins to the inner segment (IS) could lead to impaired visual responses and photoreceptor cell degeneration, causing a loss of visual function. We showed involvement of an unconventional motor protein, MYO1C, in the proper localization of rhodopsin to the OS, where loss of MYO1C in a mammalian model caused mislocalization of rhodopsin to IS and cell bodies, leading to progressively severe retinal phenotypes. In this study, using modeling and docking analysis, we aimed to identify the protein-protein interaction sites between MYO1C and Rhodopsin to establish a hypothesis that a physical interaction between these proteins is necessary for the proper trafficking of rhodopsin and visual function.
视杆细胞和视锥细胞是脊椎动物视网膜中的光感受器神经元,对于视觉感知至关重要,其蛋白质的正确定位和区室化对于光转导和视觉功能至关重要。在人类视网膜疾病中,蛋白质向光感受器外节(OS)的运输不当或蛋白质错误定位到内节(IS),可能导致视觉反应受损和光感受器细胞变性,从而导致视觉功能丧失。我们发现一种非典型的运动蛋白 MYO1C 参与了视蛋白向 OS 的正确定位,在哺乳动物模型中 MYO1C 的缺失导致视蛋白错误定位到 IS 和细胞体,导致进行性严重的视网膜表型。在这项研究中,我们使用建模和对接分析,旨在确定 MYO1C 和视蛋白之间的蛋白-蛋白相互作用位点,以建立一个假设,即这些蛋白质之间的物理相互作用对于视蛋白的正确运输和视觉功能是必要的。