The structural basis for Z $α_1$-antitrypsin polymerization in the liver
| Autor: | Bibek Gooptu, Adam Redzej, Ibrahim Aldobiyan, Elena V. Orlova, David H. Adams, James A. Irving, S. Tamir Rashid, Nina Heyer-Chauhan, Gary M. Reynolds, Magd Badaoui, Alistair M. Jagger, Sarah V. Faull, Emma L. K. Elliston, Elena Miranda, David A. Lomas |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
animal structures
Alpha-1 antitrypsin polymers Mutant Diseases and Disorders liver 03 medical and health sciences 0302 clinical medicine Structural Biology Molecule Research Articles 030304 developmental biology chemistry.chemical_classification alpha-1 antitrypsin deficiency 0303 health sciences Multidisciplinary Chemistry SciAdv r-articles Polymer Transplantation α1 antitrypsin Polymerization 030220 oncology & carcinogenesis Electron micrographs Biophysics ddc:500 Ex vivo Research Article |
| Zdroj: | 'Science Advances ', vol: 6, pages: eabc1370-1-eabc1370-15 (2020) Science Advances Science advances 6(43), eabc1370 (1-14) (2020). doi:10.1126/sciadv.abc1370 |
| ISSN: | 2375-2548 |
| DOI: | 10.3204/pubdb-2020-04299 |
| Popis: | Science advances 6(43), eabc1370 (1-14) (2020). doi:10.1126/sciadv.abc1370 The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. α$_1$-Antitrypsin deficiency is the archetypal serpinopathy and results from the formation and deposition of mutant forms of α$_1$-antitrypsin as “polymer” chains in liver tissue. No detailed structural analysis has been performed of this material. Moreover, there is little information on the relevance of well-studied artificially induced polymers to these disease-associated molecules. We have isolated polymers from the liver tissue of Z α$_1$-antitrypsin homozygotes (E342K) who have undergone transplantation, labeled them using a Fab fragment, and performed single-particle analysis of negative-stain electron micrographs. The data show structural equivalence between heat-induced and ex vivo polymers and that the intersubunit linkage is best explained by a carboxyl-terminal domain swap between molecules of α$_1$-antitrypsin. Published by Assoc., Washington, DC [u.a.] |
| Databáze: | OpenAIRE |
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