6qu9

Publication Abstract from PubMed

The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. alpha1-Antitrypsin deficiency is the archetypal serpinopathy and results from the formation and deposition of mutant forms of alpha1-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 alpha1-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 alpha1-antitrypsin.

The structural basis for Z alpha1-antitrypsin polymerization in the liver.,Faull SV, Elliston ELK, Gooptu B, Jagger AM, Aldobiyan I, Redzej A, Badaoui M, Heyer-Chauhan N, Rashid ST, Reynolds GM, Adams DH, Miranda E, Orlova EV, Irving JA, Lomas DA Sci Adv. 2020 Oct 21;6(43). pii: 6/43/eabc1370. doi: 10.1126/sciadv.abc1370., Print 2020 Oct. PMID:33087346^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.