人LRRC8单颗粒冷冻电镜成像数据集

体积调节阴离子通道LRRC8的N端延伸（NTE）与孔的形成、离子渗透和通道激活有关。在这里，我们报道了人类LRRC8A通道在2.78Å分辨率下的低温电子显微镜结构，其中首次揭示了NTE的原子细节。NTE的N和C半段分别参与了离子通道跨膜区窄颈和宽基的构建。N端延伸的N半段的带电残基Arg-8和Glu-6分别调节卤化物阴离子的阴离子渗透选择性和渗透比。N端延伸的C半段的极性残基与细胞质侧内环的极性残基和带电残基相互作用。假定的脂质分子在亚单位间裂隙中被确定。N端延伸的N和C半段以及脂质分子有助于孔结构域的紧密组装。我们也提出了LRRC8通道的激活模型。The N-terminal extension (NTE) of volume-regulated anion channel LRRC8 is involved in pore formation, ion permeation, and channel activation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human LRRC8A channel at 2.78 Å resolution, which for the first time reveals the atomic details of the NTE. The N- and C-terminal halves of the NTE participate in constructing the narrow neck and wide base of the ion channel transmembrane domain, respectively. The charged residues Arg-8 and Glu-6 within the N-terminal half of the NTE respectively regulate the anion permeation selectivity and permeation ratio of halide anions. The polar residues in the C-terminal half of the NTE interact with polar and charged residues of the intracellular loop on the cytoplasmic side. Putative lipid molecules were identified in the inter-subunit clefts. The N- and C-terminal halves of the NTE, together with the lipid molecules, contribute to the tight assembly of the pore domain. We also propose an activation model for the LRRC8 channel.

搜集汇总

背景与挑战

背景概述

该数据集提供了人类LRRC8A体积调节阴离子通道在2.78Å分辨率下的单颗粒冷冻电镜结构，首次揭示了N端延伸的原子细节。N端延伸的N和C半段分别参与离子通道结构的构建，并调节阴离子渗透选择性，同时提出了LRRC8通道的激活模型。