The protein organization of a red blood cell.

The protein organization of a red blood cell.
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DOI:
10.1016/j.celrep.2022.111103
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发表时间:
2022-07-19
期刊:
影响因子:
8.8
通讯作者:
Marcotte, Edward M.
Marcotte, Edward M.
中科院分区:
生物学1区
文献类型:
--
作者:
Sae-Lee, Wisath;McCafferty, Caitlyn L.;Verbeke, Eric J.;Havugimana, Pierre C.;Papoulas, Ophelia;McWhite, Claire D.;Houser, John R.;Vanuytsel, Kim;Murphy, George J.;Drew, Kevin;Emili, Andrew;Taylor, David W.;Marcotte, Edward M.

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红细胞(RBC,红细胞)是最简单的原代人类细胞,缺乏细胞核和主要细胞器,而是采用约一千种蛋白质来动态控制细胞功能和形态以响应生理线索。在这项研究中,我们使用定量质谱和机器学习定义了一个典型的RBC蛋白质组和相互作用组。我们的数据揭示了红细胞相互作用组主要由蛋白质稳态,氧化还原生物学,细胞骨架动力学和碳代谢。我们通过电子显微镜和化学交联验证了蛋白质复合物,并利用这些数据建立了锚蛋白/带3/带4.2复合物的3D结构模型,该复合物将血影蛋白细胞骨架连接到RBC膜。该模型表明锚蛋白的弹簧样压缩可能有助于特征性RBC细胞形状和柔性。总之,我们的研究提供了对人类红细胞全球蛋白质组织的深入了解,并为未来的研究提供了全面的资源。
Red blood cells (RBCs, erythrocytes) are the simplest primary human cells, lacking nuclei and major organelles, and instead employing about a thousand proteins to dynamically control cellular function and morphology in response to physiological cues. In this study, we defined a canonical RBC proteome and interactome using quantitative mass spectrometry and machine learning. Our data reveal an RBC interactome dominated by protein homeostasis, redox biology, cytoskeletal dynamics, and carbon metabolism. We validated protein complexes through electron microscopy and chemical crosslinking, and with these data, built 3D structural models of the ankyrin/Band 3/Band 4.2 complex that bridges the spectrin cytoskeleton to the RBC membrane. The model suggests spring-like compression of ankyrin may contribute to the characteristic RBC cell shape and flexibility. Taken together, our study provides an in-depth view of the global protein organization of human RBCs and serves as a comprehensive resource for future research.
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