Multiscale photocatalytic proximity labeling reveals cell surface neighbors on and between cells

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2024-07-19 DOI:10.1126/science.adl5763

Zhi Lin, Kaitlin Schaefer, Irene Lui, Zi Yao, Andrea Fossati, Danielle L. Swaney, Ajikarunia Palar, Andrej Sali, James A. Wells

引用次数: 0

Abstract

Proximity labeling proteomics (PLP) strategies are powerful approaches to yield snapshots of protein neighborhoods. Here, we describe a multiscale PLP method with adjustable resolution that uses a commercially available photocatalyst, Eosin Y, which upon visible light illumination activates different photo-probes with a range of labeling radii. We applied this platform to profile neighborhoods of the oncogenic epidermal growth factor receptor and orthogonally validated more than 20 neighbors using immunoassays and AlphaFold-Multimer prediction. We further profiled the protein neighborhoods of cell-cell synapses induced by bispecific T cell engagers and chimeric antigen receptor T cells. This integrated multiscale PLP platform maps local and distal protein networks on and between cell surfaces, which will aid in the systematic construction of the cell surface interactome, revealing horizontal signaling partners and reveal new immunotherapeutic opportunities.

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多尺度光催化接近标记揭示了细胞上和细胞间的细胞表面邻居。

近距离标记蛋白质组学（PLP）策略是获得蛋白质邻域快照的有力方法。在这里，我们介绍了一种分辨率可调的多尺度 PLP 方法，该方法使用了一种市售的光催化剂 Eosin Y，在可见光照射下可激活不同标记半径的光致发光物。我们将该平台用于分析致癌表皮生长因子受体的邻域，并利用免疫测定和 AlphaFold-Multimer 预测对 20 多个邻域进行了正交验证。我们进一步分析了由双特异性 T 细胞啮合因子和嵌合抗原受体 T 细胞诱导的细胞-细胞突触的蛋白质邻域。这个集成的多尺度 PLP 平台绘制了细胞表面和细胞表面之间的局部和远端蛋白质网络，这将有助于系统地构建细胞表面相互作用组，揭示水平信号传导伙伴，发现新的免疫治疗机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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