{"doi":"10.1002/pro.4791","title":"One‐step site‐specific <i>S</i>‐alkylation of full‐length caveolin‐1: Lipidation modulates the topology of its <i>C</i>‐terminal domain","abstract":"Caveolin-1 is an integral membrane protein that is known to acquire a number of posttranslational modifications upon trafficking to the plasma membrane. In particular, caveolin-1 is palmitoylated at three cysteine residues (C133, C143, and C156) located within the C-terminal domain of the protein which could have structural and topological implications. Herein, a reliable preparation of full-length S-alkylated caveolin-1, which closely mimics the palmitoylation observed in vivo, is described. HPLC and ESI-LC-MS analyses verified the addition of the C16 alkyl groups to caveolin-1 constructs containing one (C133), two (C133 and C143), and three (C133, C143, and C156) cysteine residues. Circular dichroism spectroscopy analysis of the constructs revealed that S-alkylation does not significantly affect the global helicity of the protein; however, molecular dynamics simulations revealed that there were local regions where the helicity was altered positively or negatively by S-alkylation. In addition, the simulations showed that lipidation tames the topological promiscuity of the C-terminal domain, resulting in a disposition within the bilayer characterized by increased depth.","journal":"Protein Science","year":2023,"id":380447,"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":0.9599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1145859,"name":"Alain Rousseau","orcid":null,"position":1,"is_corresponding":false},{"id":1145860,"name":"Thomas V. Perone","orcid":null,"position":2,"is_corresponding":false},{"id":1145861,"name":"David M. LaGatta","orcid":null,"position":3,"is_corresponding":false},{"id":1145862,"name":"Chan Hong","orcid":null,"position":4,"is_corresponding":false},{"id":448074,"name":"Kyle T. Root","orcid":null,"position":5,"is_corresponding":false},{"id":682006,"name":"Soohyung Park","orcid":"0000-0002-4883-3031","position":6,"is_corresponding":false},{"id":1145495,"name":"René Fuanta","orcid":"0000-0003-0163-717X","position":7,"is_corresponding":false},{"id":56772,"name":"Wonpil Im","orcid":"0000-0001-5642-6041","position":8,"is_corresponding":false},{"id":446942,"name":"Kerney Jebrell Glover","orcid":"0000-0002-1867-4965","position":9,"is_corresponding":false},{"id":761227,"name":"Jeffrey A. Julien","orcid":"0000-0002-0831-9986","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:17:00.789848Z","pmid":"37801623","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":[]}