{"doi":"10.1021/jacsau.4c00988","title":"SMAP3-ID for Identification of Endogenous Protein–Protein Interactions Reveals Regulation of Mitochondrial Activity by Lamins","abstract":"High Resolution Image Download MS PowerPoint Slide 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 ( s mall- m olecule- a ssisted id entification of p rotein– p rotein interactions through p roximity) 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 bioorthogonal click reaction with a trifunctional chemical probe, and a final photo-cross-linking reaction to covalently capture the interacting proteins. Using the SMAP3-ID method and nuclear lamins as an example, we identified numerous lamin interactors in native cells. Significantly, we identified a number of mitochondrial enzymes as novel lamin A (LA) interactors. The interactions between mitochondrial enzymes and LA were further validated, which provides mechanistic insights underlying the metabolic alterations caused by mutations in LA. Furthermore, our previously described small-molecule ligand for LA, LBL1, also induced changes in mitochondrial activity and cellular bioenergetic organization. We conclude that SMAP3-ID is a potentially powerful and generalizable method to identify protein–protein interactions in the native cellular environment.","journal":"JACS Au","year":2025,"id":520343,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1389910,"name":"Jian Wang","orcid":"0000-0003-0806-9590","position":1,"is_corresponding":false},{"id":1390300,"name":"Francis Dhoro","orcid":null,"position":2,"is_corresponding":false},{"id":767840,"name":"Bo Chao","orcid":"0000-0002-4186-8354","position":3,"is_corresponding":false},{"id":293124,"name":"Ashok P. Reddy","orcid":"0000-0003-1967-6927","position":4,"is_corresponding":false},{"id":572391,"name":"Stefanie Kaech","orcid":"0000-0002-6246-6434","position":5,"is_corresponding":false},{"id":141412,"name":"Larry L. David","orcid":null,"position":6,"is_corresponding":false},{"id":255386,"name":"Xiangshu Xiao","orcid":"0000-0001-9520-1371","position":7,"is_corresponding":false},{"id":922018,"name":"Bingbing X. Li","orcid":"0000-0001-8259-9448","position":8,"is_corresponding":false},{"id":871177,"name":"Julia T. Warren","orcid":"0000-0003-2017-6444","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:49:28.470782Z","pmid":"39886595","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}