Nano-scale resolution of native retinal rod disk membranes reveals differences in lipid composition.

Nano-scale resolution of native retinal rod disk membranes reveals differences in lipid composition.
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天然视网膜杆盘膜的纳米级分辨率揭示了脂质成分的差异。

DOI:
10.1083/jcb.202101063
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发表时间:
2021-08-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Palczewski K
Palczewski K
中科院分区:
其他
文献类型:
--
作者:
Sander CL;Sears AE;Pinto AFM;Choi EH;Kahremany S;Gao F;Salom D;Jin H;Pardon E;Suh S;Dong Z;Steyaert J;Saghatelian A;Skowronska-Krawczyk D;Kiser PD;Palczewski K

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Sander等人分析了天然来源感光盘的脂质组成,发现中心和边缘区域之间的脂肪酸不饱和度和链长存在很大差异。他们使用纳米抗体和抗体选择性地共纯化SMALP中每个区域的膜蛋白和脂质。光感受器依赖于不同的膜隔室来支持它们的专门功能。与蛋白质定位不同,由于难以分离结构域特异性样品,膜含量的关键差异的鉴定尚未扩展到脂质。我们已经克服了这一点,通过使用SMA coimmunopurify膜蛋白和它们的天然脂质从两个区域的感光器ROS盘。对每个样品的共纯化脂质进行非靶向脂质组学和脂肪酸分析。中心(视紫红质)和边缘(ABCA 4和PRPH 2/ROM 1)样品之间的广泛差异包括较低的PC与PE比率以及中心相对于边缘区域增加的LC-和VLC-PUFA,边缘区域富含较短的饱和FA。两种边缘样品之间相对较少的差异可能反映了特定的蛋白质-脂质相互作用。ROS盘脂质组成的高分辨率分析为复杂的膜结构和蛋白质活性如何在ROS内平衡提供了新的见解,并为未来研究其他复杂的细胞结构提供了模型。
Sander et al. have parsed the lipid composition of native-source photoreceptor disks and found large differences in fatty acid unsaturation and chain length between the center and rim regions. They selectively copurified membrane proteins and lipids from each region in SMALPs using nanobodies and antibodies. Photoreceptors rely on distinct membrane compartments to support their specialized function. Unlike protein localization, identification of critical differences in membrane content has not yet been expanded to lipids, due to the difficulty of isolating domain-specific samples. We have overcome this by using SMA to coimmunopurify membrane proteins and their native lipids from two regions of photoreceptor ROS disks. Each sample's copurified lipids were subjected to untargeted lipidomic and fatty acid analysis. Extensive differences between center (rhodopsin) and rim (ABCA4 and PRPH2/ROM1) samples included a lower PC to PE ratio and increased LC- and VLC-PUFAs in the center relative to the rim region, which was enriched in shorter, saturated FAs. The comparatively few differences between the two rim samples likely reflect specific protein–lipid interactions. High-resolution profiling of the ROS disk lipid composition gives new insights into how intricate membrane structure and protein activity are balanced within the ROS, and provides a model for future studies of other complex cellular structures.
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