Istituto di Chimica del Riconoscimento Molecolare, CNR (ICRM-CNR), via Mario Bianco 9, 20131 Milan, Italy.
Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ Cambridge, UK.
Prog Biophys Mol Biol. 2019 Jan;141:3-14. doi: 10.1016/j.pbiomolbio.2018.07.001. Epub 2018 Jul 2.
Fragile X Mental Retardation Protein (FMRP) is a RNA-binding protein (RBP) known to control different steps of mRNA metabolism, even though its complete function is not fully understood yet. Lack or mutations of FMRP lead to Fragile X Syndrome (FXS), the most common form of inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). It is well established that FMRP has a multi-domain architecture, a feature that allows this RBP to be engaged in a large interaction network with numerous proteins and mRNAs or non-coding RNAs. Insights into the three-dimensional (3D) structure of parts of its three domains (N-terminus, central domain and C-terminus) were obtained using Nuclear Magnetic Resonance and X-ray diffraction, but the complete 3D arrangement of each domain with respect to the others is still missing. Here, we review the structural features of FMRP and of the network of its protein and RNA interactions. Understanding these aspects is the first necessary step towards the design of novel compounds for new therapeutic interventions in FXS.
脆性 X 智力低下蛋白 (FMRP) 是一种 RNA 结合蛋白 (RBP)，已知其能够控制 mRNA 代谢的不同步骤，尽管其完整功能尚未完全了解。FMRP 的缺失或突变会导致脆性 X 综合征 (FXS)，这是最常见的遗传性智力障碍形式，也是自闭症谱系障碍 (ASD) 的主要单基因病因。已经证实 FMRP 具有多结构域架构，这一特性使其能够与许多蛋白质、mRNA 或非编码 RNA 形成庞大的相互作用网络。使用核磁共振和 X 射线衍射技术获得了其三个结构域（N 端、中心结构域和 C 端）部分的三维 (3D) 结构，但各结构域相对于其他结构域的完整 3D 排列仍然缺失。本文综述了 FMRP 及其蛋白质和 RNA 相互作用网络的结构特征。理解这些方面是设计用于 FXS 新型治疗干预的新型化合物的首要必要步骤。
