Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Autophagy. 2020 Apr;16(4):585-588. doi: 10.1080/15548627.2020.1719725. Epub 2020 Jan 29.
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 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. ER, endoplasmic reticulum; IDPR, intrinsically disordered protein region; LIR, LC3-interacting region; MD, molecular dynamics; RHD, reticulon-homology domain; TM, transmembrane.
选择性网质溶酶体的自噬受体 RETREG1/FAM134B 对于内质网的维持是必不可少的，其功能障碍与神经元紊乱、血管性痴呆或病毒感染有关。该蛋白由具有内质网同源结构域（RHD）组成，其 N 端和 C 端均被无规卷曲蛋白区域（IDPR）包围，C 端 IDPR 带有与 LC3 相互作用的必需 LC3 相互作用区域（LIR）基序，用于与 LC3 相互作用。RETREG1 的 RHD 被认为在膜重塑中发挥作用，但由于目前缺乏该结构域的已知 3D 结构，研究人员无法深入了解 RETREG1 RHD 如何弯曲膜，从而促进网质溶酶体。本期编辑精选文章中描述的 Bhaskara 等人的最新研究使用分子动力学（MD）模拟创建了 RETREG1 RHD 的结构模型。MD 模拟和脂质体重塑实验揭示了 RHD 结构域如何作用于内质网膜，并与 C 端 IDPR 一起执行 RETREG1 在选择性网质溶酶体中的功能。ER，内质网；IDPR，无规卷曲蛋白区域；LIR，LC3 相互作用区域；MD，分子动力学；RHD，内质网同源结构域；TM，跨膜。
