关键词: Atomic force microscopy (AFM) Constitutive activity G protein-coupled receptor (GPCR) Phototransduction Rhodopsin

Mesh : Rhodopsin / analysis chemistry Cell Membrane / chemistry Microscopy, Atomic Force Reactive Oxygen Species Rod Cell Outer Segment / chemistry

来  源:   DOI:10.1002/tcr.202300113   PDF(Pubmed)

Abstract:
Rhodopsin is a G protein-coupled receptor (GPCR) present in the rod outer segment (ROS) of photoreceptor cells that initiates the phototransduction cascade required for scotopic vision. Due to the remarkable advancements in technological tools, the chemistry of rhodopsin has begun to unravel especially over the past few decades, but mostly at the ensemble scale. Atomic force microscopy (AFM) is a tool capable of providing critical information from a single-molecule point of view. In this regard, to bolster our understanding of rhodopsin at the nanoscale level, AFM-based imaging, force spectroscopy, and nano-indentation techniques were employed on ROS disc membranes containing rhodopsin, isolated from vertebrate species both in normal and diseased states. These AFM studies on samples from native retinal tissue have provided fundamental insights into the structure and function of rhodopsin under normal and dysfunctional states. We review here the findings from these AFM studies that provide important insights on the supramolecular organization of rhodopsin within the membrane and factors that contribute to this organization, the molecular interactions stabilizing the structure of the receptor and factors that can modify those interactions, and the mechanism underlying constitutive activity in the receptor that can cause disease.
摘要:
视紫红质是存在于感光细胞的杆外段(ROS)中的G蛋白偶联受体(GPCR),可引发暗视所需的光转导级联。由于技术工具的显着进步,特别是在过去的几十年里,视紫红质的化学性质已经开始瓦解,但主要是在整体规模上。原子力显微镜(AFM)是一种能够从单分子角度提供关键信息的工具。在这方面,为了加强我们对纳米水平视紫红质的理解,基于AFM的成像,力光谱学,并在含有视紫红质的ROS椎间盘膜上采用纳米压痕技术,从正常和患病状态的脊椎动物中分离出来。这些对来自天然视网膜组织的样品的AFM研究提供了对视紫红质在正常和功能失调状态下的结构和功能的基本见解。我们在这里回顾了这些AFM研究的发现,这些研究提供了关于膜内视紫红质的超分子组织和有助于这种组织的因素的重要见解。稳定受体结构的分子相互作用和可以改变这些相互作用的因素,以及可能导致疾病的受体中组成活性的潜在机制。
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