@article{8ca159a1527441a1a6c93dfda4ebce2f,
title = "The structural basis for Z α1-antitrypsin polymerization in the liver",
abstract = "The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. α1-Antitrypsin deficiency is the archetypal serpinopathy and results from the formation and deposition of mutant forms of α1-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 α1-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 α1-antitrypsin.",
author = "Faull, {Sarah V.} and Elliston, {Emma L.K.} and Bibek Gooptu and Jagger, {Alistair M.} and Ibrahim Aldobiyan and Adam Redzej and Magd Badaoui and Nina Heyer-Chauhan and Rashid, {S. Tamir} and Reynolds, {Gary M.} and Adams, {David H.} and Elena Miranda and Orlova, {Elena V.} and Irving, {James A.} and Lomas, {David A.}",
note = "Funding Information: This work was supported by a grant from the Medical Research Council (UK) to D.A.L. (MR/N024842/1, also supporting J.A.I. as RCo-I and B.G. as Co-I) and the NIHR UCLH Biomedical Research Centre. D.A.L. is an NIHR Senior Investigator. S.V.F. was the recipient of an EPSRC/GSK CASE studentship. E.L.K.E. was the recipient of a Wellcome Trust Biomedical Research Studentship to the ISMB. B.G. was supported for this work by a Wellcome Trust Intermediate Clinical Fellowship and is currently supported by the NIHR Leicester Biomedical Research Centre. This work was funded, in part, by an Alpha-1 Foundation grant to J.A.I. The equipment used at the ISMB/Birkbeck EM Laboratory was funded by the Wellcome Trust (grants 101488 and 058736). Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",
year = "2020",
month = oct,
day = "23",
doi = "10.1126/sciadv.abc1370",
language = "English",
volume = "6",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "43",
}