{"doi":"10.1074/jbc.ra120.014442","title":"High-speed atomic force microscopy directly visualizes conformational dynamics of the HIV Vif protein in complex with three host proteins","abstract":"Vif (viral infectivity factor) is a protein that is essential for the replication of the HIV-1 virus. The key function of Vif is to disrupt the antiviral activity of host APOBEC3 (apolipoprotein B mRNA-editing enzyme catalytic subunit 3) proteins, which mutate viral nucleic acids. Inside the cell, Vif binds to the host cell proteins Elongin-C, Elongin-B, and core-binding factor subunit β, forming a four-protein complex called VCBC. The structure of VCBC–Cullin5 has recently been solved by X-ray crystallography, and, using molecular dynamics simulations, the dynamics of VCBC have been characterized. Here, we applied time-lapse high-speed atomic force microscopy to visualize the conformational changes of the VCBC complex. We determined the three most favorable conformations of this complex, which we identified as the triangle, dumbbell, and globular structures. Moreover, we characterized the dynamics of each of these structures. Our data revealed the very dynamic behavior of all of them, with the triangle and dumbbell structures being the most dynamic. These findings provide insight into the structure and dynamics of the VCBC complex and may support efforts to improve HIV treatment, because Vif is essential for virus survival in the cell. Vif (viral infectivity factor) is a protein that is essential for the replication of the HIV-1 virus. The key function of Vif is to disrupt the antiviral activity of host APOBEC3 (apolipoprotein B mRNA-editing enzyme catalytic subunit 3) proteins, which mutate viral nucleic acids. Inside the cell, Vif binds to the host cell proteins Elongin-C, Elongin-B, and core-binding factor subunit β, forming a four-protein complex called VCBC. The structure of VCBC–Cullin5 has recently been solved by X-ray crystallography, and, using molecular dynamics simulations, the dynamics of VCBC have been characterized. Here, we applied time-lapse high-speed atomic force microscopy to visualize the conformational changes of the VCBC complex. We determined the three most favorable conformations of this complex, which we identified as the triangle, dumbbell, and globular structures. Moreover, we characterized the dynamics of each of these structures. Our data revealed the very dynamic behavior of all of them, with the triangle and dumbbell structures being the most dynamic. These findings provide insight into the structure and dynamics of the VCBC complex and may support efforts to improve HIV treatment, because Vif is essential for virus survival in the cell. HIV is an enveloped retrovirus that causes AIDS in humans (1Gallo R.C. Sarin P.S. Gelmann E.P. Robert-Guroff M. Richardson E. Kalyanaraman V.S. Mann D. Sidhu G.D. Stahl R.E. Zolla-Pazner S. Leibowitch J. Popovic M. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS).Science. 1983; 220 (6601823): 865-86710.1126/science.6601823Crossref PubMed Scopus (801) Google Scholar). The virus particle contains two identical RNA copies and structural and replication enzymes for virus reproduction (2Sierra S. Kupfer B. Kaiser R. Basics of the virology of HIV-1 and its replication.J. Clin. Virol. 2005; 34 (16198625): 233-24410.1016/j.jcv.2005.09.004Crossref PubMed Scopus (98) Google Scholar). One of the critical proteins needed for the virus survival is Vif (viral infectivity factor) (3Cullen B.R. HIV-1 Vif: counteracting innate antiretroviral defenses.Mol. Ther. 2003; 8 (14565218): 525-52710.1016/j.ymthe.2003.08.010Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar). Vif, a small and unstructured 23-kDa protein (4Reingewertz T.H. Shalev D.E. Friedler A. Structural disorder in the HIV-1 Vif protein and interaction-dependent gain of structure.Protein Pept. Lett. 2010; 17 (20450485): 988-99810.2174/092986610791498876Crossref PubMed Scopus (20) Google Scholar, 5Dyson H.J. Making sense of intrinsically disordered proteins.Biophys. J. 2016; 110 (26958875): 1013-101610.1016/j.bpj.2016.01.030Abstract Full Text Full Text PDF PubMed Sco","journal":"Journal of Biological Chemistry","year":2020,"id":84100,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.964,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":111787,"name":"Luda S. Shlyakhtenko","orcid":null,"position":1,"is_corresponding":false},{"id":373682,"name":"Yuri L. Lyubchenko","orcid":"0000-0001-9721-8302","position":2,"is_corresponding":false},{"id":433109,"name":"Yangang Pan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T21:54:50.827092Z","pmid":"32587092","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":[]}