biostudies-literatureWarren JNIBIB NIH HHSNEI NIH HHSNCI NIH HHSNIGMS NIH HHS302-319https://www.ebi.ac.uk/biostudies/studies/S-EPMC11775715biostudies-literatureUnknown5(1)Proteins regulate biological functions through the formation of distinct protein complexes. Identification and characterization of these protein-protein interactions are critical to deciphering their mechanism of action. Different antibody-based or cross-linking-based methods have been developed to identify the protein-protein interactions. However, these methods require genetic engineering or other means to disrupt the native environments. To circumvent this limitation, we introduce here SMAP3-ID (small-molecule-assisted identification of protein-protein interactions through proximity) method to identify protein-protein interactions in native cellular environment. This method combines a selective ligand for binding to a protein of interest for photo-cross-linking, a live-cell-compatible bJACS AuSMAP3-ID for Identification of Endogenous Protein-Protein Interactions Reveals Regulation of Mitochondrial Activity by Lamins.PMC11775715R21 EB028425P30 CA069533R01 GM122820R01 CA211866R01 CA278058P30 EY010572R01 CA245964David LLPetrie SKLi BXXiao XWarren JWang JChao BDhoro FReddy AfalseSMAP3-ID for Identification of Endogenous Protein-Protein Interactions Reveals Regulation of Mitochondrial Activity by Lamins.Proteins regulate biological functions through the formation of distinct protein complexes. Identification and characterization of these protein-protein interactions are critical to deciphering their mechanism of action. Different antibody-based or cross-linking-based methods have been developed to identify the protein-protein interactions. However, these methods require genetic engineering or other means to disrupt the native environments. To circumvent this limitation, we introduce here SMAP3-ID (small-molecule-assisted identification of protein-protein interactions through proximity) method to identify protein-protein interactions in native cellular environment. This method combines a selective ligand for binding to a protein of interest for photo-cross-linking, a live-cell-compatible b2025-01-01T00:00:00Z2025 Jan2025-04-04T23:11:11.985Z2025-04-04T23:11:11.985ZS-EPMC117757153988659510.1021/jacsau.4c00988