{"doi":"10.1371/journal.ppat.1009642","title":"Structurally distinct external solvent-exposed domains drive replication of major human prions","abstract":"There is a limited understanding of structural attributes that encode the iatrogenic transmissibility and various phenotypes of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD). Here we report the detailed structural differences between major sCJD MM1, MM2, and VV2 prions determined with two complementary synchrotron hydroxyl radical footprinting techniques-mass spectrometry (MS) and conformation dependent immunoassay (CDI) with a panel of Europium-labeled antibodies. Both approaches clearly demonstrate that the phenotypically distant prions differ in a major way with regard to their structural organization, and synchrotron-generated hydroxyl radicals progressively inhibit their seeding potency in a strain and structure-specific manner. Moreover, the seeding rate of sCJD prions is primarily determined by strain-specific structural organization of solvent-exposed external domains of human prion particles that control the seeding activity. Structural characteristics of human prion strains suggest that subtle changes in the organization of surface domains play a critical role as a determinant of human prion infectivity, propagation rate, and targeting of specific brain structures.","journal":"PLoS Pathogens","year":2021,"id":190991,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":485300,"name":"Chae Kim","orcid":"0000-0003-0049-0807","position":1,"is_corresponding":false},{"id":485301,"name":"Tracy Haldiman","orcid":"0000-0002-9257-9149","position":2,"is_corresponding":false},{"id":755874,"name":"Miroslava Kacířová","orcid":"0000-0002-1478-1712","position":3,"is_corresponding":false},{"id":456391,"name":"Benlian Wang","orcid":"0000-0002-6108-0417","position":4,"is_corresponding":false},{"id":738877,"name":"Jen Bohon","orcid":"0000-0002-7664-9899","position":5,"is_corresponding":false},{"id":355234,"name":"Mark R. Chance","orcid":"0000-0002-2991-6405","position":6,"is_corresponding":false},{"id":250428,"name":"Janna Kiselar","orcid":"0000-0002-6240-7522","position":7,"is_corresponding":false},{"id":231336,"name":"Jiri Safar","orcid":"0000-0003-2209-0070","position":8,"is_corresponding":false},{"id":755873,"name":"Mohammad Khursheed Siddiqi","orcid":"0000-0002-6522-1643","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-18T23:49:31.121780Z","pmid":"34138981","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":[]}