High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials.
High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials.
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DOI：
10.1002/cbic.202200310
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发表时间：
2022-09-05
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肿瘤抑制基因（如肿瘤蛋白53（TP 53））的突变与侵袭性癌症密切相关，导致功能获得和丧失表型。虽然p53蛋白的各个结构域已被广泛研究，但全长p53的结构信息仍然不完整。功能化的微处理器芯片（微芯片）的性能服从电子显微镜允许我们可视化完整的p53组件的第一次。新的结构显示p53处于不依赖于DNA结合的非活性二聚体状态。位于蛋白质-蛋白质界面的残基对应于癌症相关热点中的修饰位点。这些区域的变化可能会放大临床突变的毒性作用。总之，这些结果有助于技术和成像方法的进步，以解码不同激活状态下的天然蛋白质模型。基于微芯片的基底和高分辨率成像技术首次用于从人类癌细胞中解析全长p53结构。
Mutations in tumor suppressor genes, such as Tumor Protein 53 (TP53), are heavily implicated in aggressive cancers giving rise to gain- and loss-of-function phenotypes. While individual domains of the p53 protein have been studied extensively, structural information for full-length p53 remains incomplete. Functionalized microprocessor chips (microchips) with properties amenable to electron microscopy permitted us to visualize complete p53 assemblies for the first time. The new structures revealed p53 in an inactive dimeric state independent of DNA binding. Residues located at the protein-protein interface corresponded with modification sites in cancer-related hot spots. Changes in these regions may amplify the toxic effects of clinical mutations. Taken together, these results contribute advances in technology and imaging approaches to decode native protein models in different states of activation. Microchip-based substrates and high-resolution imaging technology were used to resolve full-length p53 structures from human cancer cells for the first time.
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