{"doi":"10.1016/j.mcpro.2021.100132","title":"Characterization of an A3G-VifHIV-1-CRL5-CBFβ Structure Using a Cross-linking Mass Spectrometry Pipeline for Integrative Modeling of Host–Pathogen Complexes","abstract":"Structural analysis of host-pathogen protein complexes remains challenging, largely due to their structural heterogeneity. Here, we describe a pipeline for the structural characterization of these complexes using integrative structure modeling based on chemical cross-links and residue-protein contacts inferred from mutagenesis studies. We used this approach on the HIV-1 Vif protein bound to restriction factor APOBEC3G (A3G), the Cullin-5 E3 ring ligase (CRL5), and the cellular transcription factor Core Binding Factor Beta (CBFβ) to determine the structure of the (A3G-Vif-CRL5-CBFβ) complex. Using the MS-cleavable DSSO cross-linker to obtain a set of 132 cross-links within this reconstituted complex along with the atomic structures of the subunits and mutagenesis data, we computed an integrative structure model of the heptameric A3G-Vif-CRL5-CBFβ complex. The structure, which was validated using a series of tests, reveals that A3G is bound to Vif mostly through its N-terminal domain. Moreover, the model ensemble quantifies the dynamic heterogeneity of the A3G C-terminal domain and Cul5 positions. Finally, the model was used to rationalize previous structural, mutagenesis and functional data not used for modeling, including information related to the A3G-bound and unbound structures as well as mapping functional mutations to the A3G-Vif interface. The experimental and computational approach described here is generally applicable to other challenging host-pathogen protein complexes.","journal":"Molecular & Cellular Proteomics","year":2021,"id":197974,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9199,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2404,"name":"Ignacia Echeverria","orcid":"0000-0003-4717-1467","position":1,"is_corresponding":false},{"id":772531,"name":"Seung Joong Kim","orcid":"0000-0002-9490-2720","position":2,"is_corresponding":false},{"id":1345,"name":"John Von Dollen","orcid":"0000-0002-8430-7848","position":3,"is_corresponding":false},{"id":772532,"name":"Nicholas M. Chesarino","orcid":"0000-0002-3582-8508","position":4,"is_corresponding":false},{"id":572594,"name":"Yuqing Feng","orcid":"0000-0002-7156-1628","position":5,"is_corresponding":false},{"id":289624,"name":"Clinton Yu","orcid":"0000-0002-2931-5474","position":6,"is_corresponding":false},{"id":310419,"name":"Hai Minh Ta","orcid":"0000-0002-7298-6177","position":7,"is_corresponding":false},{"id":318116,"name":"Linda Chelico","orcid":"0000-0003-4673-8978","position":8,"is_corresponding":false},{"id":289627,"name":"Lan Huang","orcid":"0000-0002-3140-4687","position":9,"is_corresponding":false},{"id":366460,"name":"John D. Gross","orcid":"0000-0002-1377-4705","position":10,"is_corresponding":false},{"id":91660,"name":"Andrej Săli","orcid":"0000-0003-0435-6197","position":11,"is_corresponding":false},{"id":1363,"name":"Nevan J. Krogan","orcid":"0000-0003-4902-337X","position":12,"is_corresponding":false},{"id":103631,"name":"Robyn M. Kaake","orcid":"0000-0002-8341-3067","position":0,"is_corresponding":true}],"reference_count":183,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:50:27.616568Z","pmid":"34389466","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":[]}