{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Aldobiyan I"],"funding":["Medical Research Council","Alpha-1 Foundation (A1F)","Wellcome Trust","Saudi Arabian Cultural Bureau (SACB)"],"pagination":["e2507535122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12646233"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(46)"],"pubmed_abstract":["Originating 2 to 3 millennia ago in a Scandinavian population, the SERPINA1 Z allele (Glu342Lys) is present in up to 2.5% of populations of Northern European descent and accounts for 95% of severe α<sub>1</sub>-antitrypsin deficiency. The α<sub>1</sub>-antitrypsin Z variant self-assembles into polymer chains that deposit within hepatocytes, predisposing to liver disease. Here, the 4.0Å subunit structure of polymers isolated directly from human liver tissue has been determined using cryoelectron microscopy. Challenges of flexibility, small subunit size, heterogeneous length, and preferred orientations were mitigated using antibody Fab domains and sample preparation strategies. This structure demonstrates that the formation of polymers in vivo involves self-incorporation of an exposed struct"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["The mechanism of pathogenic α&lt;sub&gt;1&lt;/sub&gt;-antitrypsin aggregation in the human liver."],"pmcid":["PMC12646233"],"funding_grant_id":["1036784","I. Aldobiyan","MR/V034243/1","206166/Z/17/Z","202679/Z/16/Z"],"pubmed_authors":["Irving JA","Lowen SM","Aldobiyan I","Elliston ELK","Zhao L","Arold ST","Huntington B","Lomas DA","Orlova EV","Heyer-Chauhan N"],"additional_accession":[]},"is_claimable":false,"name":"The mechanism of pathogenic α&lt;sub&gt;1&lt;/sub&gt;-antitrypsin aggregation in the human liver.","description":"Originating 2 to 3 millennia ago in a Scandinavian population, the SERPINA1 Z allele (Glu342Lys) is present in up to 2.5% of populations of Northern European descent and accounts for 95% of severe α<sub>1</sub>-antitrypsin deficiency. The α<sub>1</sub>-antitrypsin Z variant self-assembles into polymer chains that deposit within hepatocytes, predisposing to liver disease. Here, the 4.0Å subunit structure of polymers isolated directly from human liver tissue has been determined using cryoelectron microscopy. Challenges of flexibility, small subunit size, heterogeneous length, and preferred orientations were mitigated using antibody Fab domains and sample preparation strategies. This structure demonstrates that the formation of polymers in vivo involves self-incorporation of an exposed struct","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-07-15T06:08:12.396Z","creation":"2026-06-30T03:20:30.401Z"},"accession":"S-EPMC12646233","cross_references":{"pubmed":["41231946"],"doi":["10.1073/pnas.2507535122"]}}