{"doi":"10.1101/2024.06.27.601044","title":"Native mass spectrometry of membrane protein-lipid interactions in different detergent environments","abstract":"Native mass spectrometry (MS) is revealing the role of specific lipids in modulating membrane protein structure and function. Membrane proteins solubilized in detergents are often introduced into the mass spectrometer; however, commonly used detergents for structural studies, such as dodecylmaltoside, tend to generate highly charged ions, leading to protein unfolding, thereby diminishing their utility for characterizing protein-lipid interactions. Thus, there is a critical need to develop approaches to investigate protein-lipid interactions in different detergents. Here, we demonstrate how charge-reducing molecules, such as spermine and trimethylamine-N-oxide, enable characterization of lipid binding to the bacterial water channel (AqpZ) and ammonia channel (AmtB) in complex with regulatory protein GlnK in different detergent environments. We find protein-lipid interactions are not only protein-dependent but can also be influenced by the detergent and type of charge-reducing molecule. AqpZ-lipid interactions are enhanced in LDAO (n-dodecyl- N , N -dimethylamine-N-oxide), whereas the interaction of AmtB-GlnK with lipids is comparable among different detergents. A fluorescent lipid binding assay also shows detergent dependence for AqpZ-lipid interactions, consistent with results from native MS. Taken together, native MS will play a pivotal role in establishing optimal experimental parameters that will be invaluable for various applications, such as drug discovery, as well as biochemical and structural investigations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488670,"datarank":0.17148701493062501,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.006695171630408563,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.006695171630408563,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":942952,"name":"Lauren Stover","orcid":"0000-0002-3554-9111","position":1,"is_corresponding":false},{"id":297717,"name":"Lie Wang","orcid":"0000-0002-9406-5168","position":2,"is_corresponding":false},{"id":1246570,"name":"Hanieh Bahramimoghaddam","orcid":null,"position":3,"is_corresponding":false},{"id":1333265,"name":"Ming Zhou","orcid":"0000-0003-4813-1424","position":4,"is_corresponding":false},{"id":323307,"name":"David H. Russell","orcid":"0000-0003-0830-3914","position":5,"is_corresponding":false},{"id":297720,"name":"Arthur Laganowsky","orcid":"0000-0001-5012-5547","position":6,"is_corresponding":false},{"id":495647,"name":"Smriti Kumar","orcid":"0000-0003-4291-222X","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:19.655720Z","pmid":"38979331","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":[]}