Pinpointing proteins To develop drugs that target a specific cell surface protein, it's helpful to know which other proteins reside in its vicinity. Geri et al. report a light-triggered labeling technique that improves the spatial resolution for this type of mapping. Specifically, they rely on a photocatalyst with a very short energy-transfer range to activate a carbene-based label that can only diffuse a short distance in water before reacting. They showcase the technique by mapping the environment of the programmed-death ligand 1 (PDL1) protein on B cell surfaces, a system of considerable interest in cancer immunotherapy. Science, this issue p. 1091 A photocatalyst that generates fast-reacting carbene labels can map adjacent cell surface proteins with high resolution. Many disease pathologies can be understood through the elucidation of localized biomolecular networks, or microenvironments. To this end, enzymatic proximity labeling platforms are broadly applied for mapping the wider spatial relationships in subcellular architectures. However, technologies that can map microenvironments with higher precision have long been sought. Here, we describe a microenvironment-mapping platform that exploits photocatalytic carbene generation to selectively identify protein-protein interactions on cell membranes, an approach we term MicroMap (μMap). By using a photocatalyst-antibody conjugate to spatially localize carbene generation, we demonstrate selective labeling of antibody binding targets and their microenvironment protein neighbors. This technique identified the constituent proteins of the programmed-death ligand 1 (PD-L1) microenvironment in live lymphocytes and selectively labeled within an immunosynaptic junction.

中文翻译：

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通过免疫细胞上的 Dexter 能量转移绘制微环境图


精确定位蛋白质 要开发针对特定细胞表面蛋白质的药物，了解其附近存在哪些其他蛋白质会很有帮助。格里等人。报告了一种光触发标记技术，可以提高此类映射的空间分辨率。具体来说，他们依靠能量转移范围非常短的光催化剂来激活卡宾基标签，该标签在反应前只能在水中扩散一小段距离。他们通过绘制 B 细胞表面程序性死亡配体 1 (PDL1) 蛋白的环境图来展示该技术，B 细胞表面是癌症免疫治疗中备受关注的一个系统。科学，本期第 14 页。 1091 一种产生快速反应卡宾标记的光催化剂可以以高分辨率绘制相邻细胞表面蛋白质的图谱。许多疾病病理可以通过局部生物分子网络或微环境的阐明来理解。为此，酶促邻近标记平台被广泛应用于绘制亚细胞结构中更广泛的空间关系。然而，长期以来人们一直在寻求能够更高精度地绘制微环境图的技术。在这里，我们描述了一种微环境绘图平台，该平台利用光催化卡宾生成来选择性地识别细胞膜上的蛋白质-蛋白质相互作用，我们将这种方法称为 MicroMap (μMap)。通过使用光催化剂-抗体缀合物对卡宾的生成进行空间定位，我们证明了抗体结合靶标及其微环境蛋白质邻居的选择性标记。该技术鉴定了活淋巴细胞中程序性死亡配体 1 (PD-L1) 微环境的组成蛋白，并在免疫突触连接内进行选择性标记。