{"doi":"10.1101/2020.11.16.385856","title":"Novel quaternary structures of the human prion protein globular domain","abstract":"Abstract Prion disease is caused by the misfolding of the cellular prion protein, PrP C , into a self-templating conformer, PrP Sc . Nuclear magnetic resonance (NMR) and X-ray crystallography revealed the 3D structure of the globular domain of PrP C and the possibility of its dimerization via an interchain disulfide bridge that forms due to domain swap or by non-covalent association of two monomers. On the contrary, PrP Sc is composed by a complex and heterogeneous ensemble of poorly defined conformations and quaternary arrangements that are related to different patterns of neurotoxicity. Targeting PrP C with molecules that stabilize the native conformation of its globular domain emerged as a promising approach to develop anti-prion therapies. One of the advantages of this approach is employing structure-based drug discovery methods to PrP C . Thus, it is essential to expand our structural knowledge about PrP C as much as possible to aid such drug discovery efforts. In this work, we report a crystallographic structure of the globular domain of human PrP C that shows a novel dimeric form and a novel oligomeric arrangement. We use molecular dynamics simulations to explore its structural dynamics and stability and discuss potential implications of these new quaternary structures to the conversion process.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":127690,"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":0.9563,"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":491945,"name":"V.L. Rangel","orcid":"0000-0002-7580-3452","position":1,"is_corresponding":false},{"id":577099,"name":"Francesca A. Pavlovici","orcid":"0000-0002-1611-5035","position":2,"is_corresponding":false},{"id":325139,"name":"Kamel El Omari","orcid":"0000-0003-3506-6045","position":3,"is_corresponding":false},{"id":277862,"name":"Armin Wagner","orcid":"0000-0001-8995-7324","position":4,"is_corresponding":false},{"id":552153,"name":"J. Brandão-Neto","orcid":"0000-0001-6015-320X","position":5,"is_corresponding":false},{"id":577100,"name":"R. Talon","orcid":"0000-0003-1123-7241","position":6,"is_corresponding":false},{"id":552166,"name":"F. von Delft","orcid":"0000-0003-0378-0017","position":7,"is_corresponding":false},{"id":491939,"name":"Andrew G. Reidenbach","orcid":"0000-0001-8421-5022","position":8,"is_corresponding":false},{"id":260620,"name":"Sonia M. Vallabh","orcid":"0000-0003-3824-2702","position":9,"is_corresponding":false},{"id":996,"name":"Eric Vallabh Minikel","orcid":"0000-0003-2206-1608","position":10,"is_corresponding":false},{"id":227629,"name":"Stuart L. Schreiber","orcid":"0000-0003-1922-7558","position":11,"is_corresponding":false},{"id":491948,"name":"Maria Cristina Nonato","orcid":"0000-0002-4916-1505","position":12,"is_corresponding":false},{"id":577098,"name":"Leandro Oliveira Bortot","orcid":"0000-0002-0915-8205","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:15:34.966380Z","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":[]}