The autophagy receptor for selective reticulophagy, RETREG1/FAM134B is essential for ER maintenance, and its dysfunction is associated with neuronal disorders, vascular dementia, or viral infections. The protein consists of the reticulon-homology domain (RHD) that is flanked at the N- and C-termini by an intrinsically disordered protein region (IDPR), where the C terminal IDPR carries the indispensable LC3-interacting region (LIR) motif for the interaction with LC3. The RHD of RETREG1 is presumed to play a role in membrane remodeling, but the absence of a known 3D structure of this domain so far prevented researchers from gaining mechanistic insights into how the RETREG1 RHD curves membranes, and thereby facilities reticulophagy. The recent study by Bhaskara et al., which is described in this editor's corner article, used molecular dynamics (MD) simulations to create a structural model of the RETREG1 RHD. MD simulations along with in vitro liposome remodeling experiments reveal how the RHD domain acts on the ER membrane and, in concert with the C terminal IDPR, executes the function of RETREG1 in selective reticulophagy.Abbreviations: ER, endoplasmic reticulum; IDPR, intrinsically disordered protein region; LIR, LC3-interacting region; MD, molecular dynamics; RHD, reticulon-homology domain; TM, transmembrane.

中文翻译：

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分子动力学模拟揭示了自噬受体RETREG1 / FAM134B的网状同源结构域如何重塑膜以实现有效的选择性网状化。

选择性网状化的自噬受体RETREG1 / FAM134B对于维持ER是必不可少的，其功能障碍与神经元疾病，血管性痴呆或病毒感染有关。该蛋白质由网状同源结构域（RHD）组成，该结构域在N和C末端两侧是一个内在无序的蛋白质区域（IDPR），其中C末端IDPR携带了不可缺少的LC3相互作用区域（LIR）基序与LC3的互动。RETREG1的RHD被认为在膜重塑中起作用，但是到目前为止，该域的3D结构缺乏已知的知识，阻止了研究人员对RETREG1 RHD如何弯曲膜从而获得网状结构的机制进行深入的研究。Bhaskara等人的最新研究（在本编辑的特辑文章中进行了介绍），使用分子动力学（MD）模拟来创建RETREG1 RHD的结构模型。MD模拟和体外脂质体重塑实验揭示了RHD结构域如何作用于ER膜，并与C末端IDPR协同作用，在选择性网状细胞学中执行RETREG1的功能。IDPR，内在无序的蛋白质区域；LIR，LC3相互作用区；医学博士，分子动力学；RHD，网状同源域；TM，跨膜。内在无序的蛋白质区域；LIR，LC3相互作用区；医学博士，分子动力学；RHD，网状同源域；TM，跨膜。内在无序的蛋白质区域；LIR，LC3相互作用区；医学博士，分子动力学；RHD，网状同源域；TM，跨膜。