The high-throughput detection of organelle composition and proteomic mapping of protein environment directly from primary tissue as well as the identification of interactors of insoluble proteins that form higher-order structures have remained challenges in biological research. We report a proximity-based labeling approach that uses an antibody to a target antigen to guide biotin deposition onto adjacent proteins in fixed cells and primary tissues, which allows proteins in close proximity to the target antigen to be captured and identified by mass spectrometry. We demonstrated the specificity and sensitivity of our method by examining the well-studied mitochondrial matrix. We then used the method to profile the dynamic interactome of lamin A/C in multiple cell and tissue types under various treatment conditions. The ability to detect proximal proteins and putative interactors in intact tissues, and to quantify changes caused by different conditions or in the presence of disease mutations, can provide a window into cell biology and disease pathogenesis.

直接从原代组织中高通量检测细胞器组成和蛋白质环境的蛋白质组学图谱以及识别形成高阶结构的不溶性蛋白质的相互作用物仍然是生物学研究中的挑战。我们报告了一种基于接近度的标记方法，该方法使用针对目标抗原的抗体来引导生物素沉积到固定细胞和原代组织中的相邻蛋白质上，从而允许通过质谱法捕获和识别与目标抗原非常接近的蛋白质。我们通过检查充分研究的线粒体基质证明了我们方法的特异性和敏感性。然后，我们使用该方法分析了在各种治疗条件下多种细胞和组织类型中核纤层蛋白 A/C 的动态相互作用组。