Proximity labeling for investigating protein-protein interactions

The study of protein complexes and protein-protein interactions is of great importance due to their fundamental roles in cellular function. Proximity labeling, often coupled with mass spectrometry, has become a powerful and versatile tool for studying protein-protein interactions by enriching and identifying proteins in the vicinity of a specified protein-of-interest. Here, we describe and compare traditional approaches to investigate protein-protein interactions to current day state-of-the-art proximity labeling methods. We focus on the wide array of proximity labeling strategies and underscore studies using diverse model systems to address numerous biological questions. In addition, we highlight current advances in mass spectrometry-based technology that exhibit promise in improving the depth and breadth of the data acquired in proximity labeling experiments. In all, we show the diversity of proximity labeling strategies and emphasize the broad range of applications and biological inquiries that can be addressed using this technology.