Department of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, TX 78712, USA.
Center for Network Systems Biology, Boston University, Boston, MA 02118, USA.
Cell Rep. 2022 Jul 19;40(3):111103. doi: 10.1016/j.celrep.2022.111103.
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 define 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 validate protein complexes through electron microscopy and chemical crosslinking and, with these data, build 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.
红细胞（RBCs）（红细胞）是最简单的人类初级细胞，缺乏细胞核和主要细胞器，而是使用大约一千种蛋白质来动态控制细胞功能和形态，以响应生理信号。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。我们的数据揭示了一个由蛋白质稳态、氧化还原生物学、细胞骨架动力学和碳代谢主导的 RBC 相互作用组。我们通过电子显微镜和化学交联验证蛋白质复合物，并利用这些数据构建连接血影蛋白细胞骨架和 RBC 膜的锚蛋白/Band 3/Band 4.2 复合物的 3D 结构模型。该模型表明，锚蛋白的类似弹簧的压缩可能有助于 RBC 细胞的特征形状和灵活性。总之，我们的研究提供了人类 RBC 中全局蛋白质组织的深入视图，并为未来的研究提供了全面的资源。
