{"doi":"10.17615/2304-bd59","title":"Structure of the HIV-1 Full-Length Capsid Protein in a Conformationally Trapped Unassembled State Induced by Small-Molecule Binding","abstract":"The capsid protein (CA) plays crucial roles in HIV-infection and replication, essential to viral maturation. The absence of high-resolution structural data on unassembled CA hinders the development of antivirals effective in inhibiting assembly. Unlike enzymes that have targetable functional substrate binding sites, the CA does not have a known site that affects catalytic or other innate activity, which can be more readily targeted in drug development efforts. We report the crystal structure of the HIV-1 CA, revealing the domain organization in context of the wild-type full-length (FL) unassembled CA. The FL CA adopts an antiparallel dimer (APD) configuration, exhibiting a domain organization sterically incompatible with capsid assembly. A small compound, generated in-situ during crystallization, is bound tightly at a hinge-site (“H-site”), indicating that binding at this interdomain region stabilizes the ADP conformation. Electron microscopy studies on nascent crystals reveal both dimeric and hexameric lattices coexisting within a single condition, in agreement with the interconvertibility of oligomeric forms and supporting the feasibility of promoting assembly-incompetent dimeric states. Solution characterization in the presence of the H-site ligand shows predominantly unassembled dimeric CA, even under conditions that promote assembly. Our structure elucidation of the HIV-1 FL CA and characterization of a potential allosteric binding site provides 3D views of an assembly-defective conformation, a state targeted in and, thus, directly relevant to, inhibitor development. Based on our findings, we propose an unprecedented means of preventing CA assembly, by ‘conformationally-trapping’ CA in assembly-incompetent conformational states, induced by H-site binding.","journal":"UNC Libraries","year":2020,"id":117233,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"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":547443,"name":"Jason Concel","orcid":null,"position":1,"is_corresponding":false},{"id":547444,"name":"Joanne I. Yeh","orcid":null,"position":2,"is_corresponding":false},{"id":546763,"name":"Haibin Shi","orcid":"0000-0001-9803-3123","position":3,"is_corresponding":false},{"id":546764,"name":"Peijun Zhang","orcid":"0000-0002-7047-7133","position":4,"is_corresponding":false},{"id":546765,"name":"Laurie Betts","orcid":"0000-0002-9869-093X","position":5,"is_corresponding":false},{"id":546766,"name":"Shoucheng Du","orcid":"0000-0002-4305-5699","position":6,"is_corresponding":false},{"id":307290,"name":"Christopher Aiken","orcid":"0000-0002-2476-4078","position":7,"is_corresponding":false},{"id":547445,"name":"Ruifeng Yang","orcid":null,"position":8,"is_corresponding":false},{"id":547442,"name":"Ahn, Jinwoo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:51.309289Z","pmid":null,"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":[]}