{"doi":"10.3390/ijms231911480","title":"A New Structural Model of Apolipoprotein B100 Based on Computational Modeling and Cross Linking","abstract":"ApoB-100 is a member of a large lipid transfer protein superfamily and is one of the main apolipoproteins found on low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) particles. Despite its clinical significance for the development of cardiovascular disease, there is limited information on apoB-100 structure. We have developed a novel method based on the \"divide and conquer\" algorithm, using PSIPRED software, by dividing apoB-100 into five subunits and 11 domains. Models of each domain were prepared using I-TASSER, DEMO, RoseTTAFold, Phyre2, and MODELLER. Subsequently, we used disuccinimidyl sulfoxide (DSSO), a new mass spectrometry cleavable cross-linker, and the known position of disulfide bonds to experimentally validate each model. We obtained 65 unique DSSO cross-links, of which 87.5% were within a 26 Å threshold in the final model. We also evaluated the positions of cysteine residues involved in the eight known disulfide bonds in apoB-100, and each pair was measured within the expected 5.6 Å constraint. Finally, multiple domains were combined by applying constraints based on detected long-range DSSO cross-links to generate five subunits, which were subsequently merged to achieve an uninterrupted architecture for apoB-100 around a lipoprotein particle. Moreover, the dynamics of apoB-100 during particle size transitions was examined by comparing VLDL and LDL computational models and using experimental cross-linking data. In addition, the proposed model of receptor ligand binding of apoB-100 provides new insights into some of its functions.","journal":"International Journal of Molecular Sciences","year":2022,"id":257912,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9416,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":461868,"name":"Scott M. Gordon","orcid":"0000-0001-9532-032X","position":1,"is_corresponding":false},{"id":312943,"name":"Denis Sviridov","orcid":null,"position":2,"is_corresponding":false},{"id":284425,"name":"Angel Aponte","orcid":"0000-0001-5684-2715","position":3,"is_corresponding":false},{"id":563097,"name":"Amanda Haymond","orcid":"0000-0002-9553-275X","position":4,"is_corresponding":false},{"id":313757,"name":"Grzegorz Piszczek","orcid":"0000-0002-5270-3678","position":5,"is_corresponding":false},{"id":586888,"name":"Diego Lucero","orcid":"0000-0003-2833-5681","position":6,"is_corresponding":false},{"id":586889,"name":"Edward B. Neufeld","orcid":"0000-0002-1248-6613","position":7,"is_corresponding":false},{"id":424768,"name":"Iosif I. Vaisman","orcid":"0000-0001-6858-1516","position":8,"is_corresponding":false},{"id":242177,"name":"Lance A. Liotta","orcid":"0000-0001-5155-7907","position":9,"is_corresponding":false},{"id":87917,"name":"Ancha Baranova","orcid":"0000-0001-6810-5982","position":10,"is_corresponding":false},{"id":311171,"name":"Alan T. Remaley","orcid":"0000-0003-2473-5549","position":11,"is_corresponding":false},{"id":908457,"name":"Kianoush Jeiran","orcid":"0000-0002-0901-034X","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T00:25:34.440699Z","pmid":"36232786","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":[]}