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-Structure paper
タイトル | The structural basis for Z α-antitrypsin polymerization in the liver. |
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ジャーナル・号・ページ | Sci Adv, Vol. 6, Issue 43, Year 2020 |
掲載日 | 2020年10月21日 |
著者 | Sarah V Faull / Emma L K Elliston / Bibek Gooptu / Alistair M Jagger / Ibrahim Aldobiyan / Adam Redzej / Magd Badaoui / Nina Heyer-Chauhan / S Tamir Rashid / Gary M Reynolds / David H Adams / Elena Miranda / Elena V Orlova / James A Irving / David A Lomas / |
PubMed 要旨 | The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. α-Antitrypsin deficiency is the archetypal ...The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. α-Antitrypsin deficiency is the archetypal serpinopathy and results from the formation and deposition of mutant forms of α-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-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-antitrypsin. |
リンク | Sci Adv / PubMed:33087346 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.9 - 26.4 Å |
構造データ | EMDB-4620: EMDB-4631: EMDB-4632: PDB-6qu9: |
化合物 | ChemComp-SO4: ChemComp-NA: ChemComp-GOL: ChemComp-HOH: |
由来 |
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キーワード | PROTEIN BINDING / Alpha-1 antitrypsin / Z variant / polymers / protein aggregation / monoclonal antibody / Fab fragment / COPD / protease inhibitor / glycoprotein / deficiency |