Fig. 1

GECX to capture protein interactions in live cells for MS identification. a Schematic illustration of the GECX-MS strategy. The Genetically Encoded Chemical Cross-linking (GECX) Uaa has proximity-enabled reactivity, which specifically reacts with the target residue (e.g., Cys) of interacting proteins only when the two proteins interact and place the Uaa in proximity to the target residue. The resultant covalent linkage captures interacting proteins in situ for subsequent identification with Mass Spectrometry (MS). The structure of the chemical cross-linking Uaa BprY and its reaction with Cys are shown at the bottom. b Schematic illustration of GECX-MS using the enrichable chemical cross-linking Uaa EB3. Structure of EB3 and its reaction with Cys via proximity-enabled reactivity, followed by labeling with biotin through the click chemistry CuAAC are shown at the bottom