Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	The mechanism of pathogenic α-antitrypsin aggregation in the human liver.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 122, Issue 46, Page e2507535122, Year 2025
Publish date	Nov 18, 2025
Authors	Ibrahim Aldobiyan / Emma L K Elliston / Narinder Heyer-Chauhan / Stefan T Arold / Lingyun Zhao / Brandon Huntington / Sarah M Lowen / Elena V Orlova / James A Irving / David A Lomas /
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- ...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-antitrypsin deficiency. The α-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 structural element (the reactive center loop) as an additional β-strand into the central β-sheet of α-antitrypsin and displacement of a C-terminal region from one subunit with incorporation into the next. Unlike amyloid aggregation, this well-folded structure partially recapitulates a conformation adopted during normal function of the protein. These perturbations to the constituent α-antitrypsin subunits of human tissue-derived polymers are consistent with a pronounced stability, their tendency toward long-chain forms, the ability of a subset to undergo canonical secretion, and the action of a class of small molecules that block polymerization in vivo.
External links	Proc Natl Acad Sci U S A / PubMed:41231946 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.2 - 3.98 Å
Structure data	EMDB-52659: A subunit of alpha-1 antitrypsin polymers isolated from ZZ explant liver tissue and decorated with conformationally nonselective Fab 9C5 Method: EM (single particle) / Resolution: 3.98 Å PDB-9gjv: Fab fragment of an antibody that recognises alpha-1 antitrypsin Method: X-RAY DIFFRACTION / Resolution: 2.2 Å PDB-9hud: Alpha-1-antitrypsin in the cleaved conformation in complex with a conformationally nonselective Fab fragment Method: X-RAY DIFFRACTION / Resolution: 2.42 Å
Chemicals	ChemComp-HOH: WATER ChemComp-EDO: 1,2-ETHANEDIOL ChemComp-GLY: GLYCINE ChemComp-CL: Unknown entry ChemComp-NA: Unknown entry ChemComp-GOL: GLYCEROL ChemComp-LYS: LYSINE
Source	homo sapiens (human) mus musculus (house mouse)
Keywords	PROTEIN BINDING / Fab fragment / antitrypsin / serpin / antibody / Complex / Cleaved Alpha-1-antitrypsin / Alpha-1-antitrypsin / Fab / Fragment antigen-binding region / Antibody antigen complex / 9C5