{"doi":"10.1038/s41467-019-13038-z","title":"Cryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis","abstract":"<jats:title>Abstract</jats:title><jats:p>ATTR amyloidosis is one of the worldwide most abundant forms of systemic amyloidosis. The disease is caused by the misfolding of transthyretin protein and the formation of amyloid deposits at different sites within the body. Here, we present a 2.97 Å cryo electron microscopy structure of a fibril purified from the tissue of a patient with hereditary Val30Met ATTR amyloidosis. The fibril consists of a single protofilament that is formed from an N-terminal and a C-terminal fragment of transthyretin. Our structure provides insights into the mechanism of misfolding and implies the formation of an early fibril state from unfolded transthyretin molecules, which upon proteolysis converts into mature ATTR amyloid fibrils.</jats:p>","journal":"Nature Communications","year":2019,"id":32782,"datarank":5.765662796502888,"base_score":5.267858159063328,"endowment":5.267858159063328,"self_citation_contribution":0.7901787238594994,"citation_network_contribution":4.975484072643389,"self_endowment_contribution":0.7901787238594994,"citer_contribution":4.975484072643389,"corpus_percentile":null,"corpus_rank":null,"citation_count":193,"citer_count":178,"citers_with_citation_signal":155,"citers_with_endowment":155,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":172893,"name":"Sebastian 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Diagnosis, Treatment, Outcomes","Protein Structure and Dynamics","Enzyme Structure and Function","Medicine","Biology","0301 basic medicine","03 medical and health sciences","Aged","Amyloid","Amyloid Neuropathies, Familial","Cryoelectron Microscopy","Humans","Male","Models, Molecular","Prealbumin","Protein Unfolding","Proteostasis Deficiencies"],"mesh_terms":["Humans","Amyloid Neuropathies, Familial","Amyloid","Prealbumin","Cryoelectron Microscopy","Models, Molecular","Aged","Male","Proteostasis Deficiencies","Protein Unfolding"],"keywords":["Transthyretin","Fibril","Amyloidosis","Amyloid fibril","Amyloid (mycology)","Proteolysis","Chemistry","Protein folding","Biophysics","Amyloid disease","Biochemistry","Medicine","Pathology","Biology","Disease","Amyloid β","Enzyme","Male","Models, Molecular","Amyloid","Amyloid Neuropathies, Familial","Science","Q","Cryoelectron Microscopy","610","Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)","Article","Humans","Prealbumin","Proteostasis Deficiencies","Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)","Aged","Protein Unfolding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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