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The Shapes of Z-alpha(1)-Antitrypsin Polymers in Solution Support the C-Terminal Domain-Swap Mechanism of Polymerization

Behrens, Manja LU ; Sendall, Timothy J.; Pedersen, Jan S.; Kjeldgaard, Morten; Huntington, James A. and Jensen, Jan K. (2014) In Biophysical Journal 107(8). p.1905-1912
Abstract
Emphysema and liver cirrhosis can be caused by the Z mutation (Glu342Lys) in the serine protease inhibitor alpha 1-antitrypsin (alpha 1AT), which is found in more than 4% of the Northern European population. Homozygotes experience deficiency in the lung concomitantly with a massive accumulation of polymers within hepatocytes, causing their destruction. Recently, it was proposed that Z-alpha 1AT polymerizes by a C-terminal domain swap. In this study, small-angle x-ray scattering (SAXS) was used to characterize Z-alpha 1AT polymers in solution. The data show that the Z-alpha 1AT trimer, tetramer, and pentamer all form ring-like structures in strong support of a common domain-swap polymerization mechanism that can lead to self-terminating... (More)
Emphysema and liver cirrhosis can be caused by the Z mutation (Glu342Lys) in the serine protease inhibitor alpha 1-antitrypsin (alpha 1AT), which is found in more than 4% of the Northern European population. Homozygotes experience deficiency in the lung concomitantly with a massive accumulation of polymers within hepatocytes, causing their destruction. Recently, it was proposed that Z-alpha 1AT polymerizes by a C-terminal domain swap. In this study, small-angle x-ray scattering (SAXS) was used to characterize Z-alpha 1AT polymers in solution. The data show that the Z-alpha 1AT trimer, tetramer, and pentamer all form ring-like structures in strong support of a common domain-swap polymerization mechanism that can lead to self-terminating polymers. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biophysical Journal
volume
107
issue
8
pages
1905 - 1912
publisher
Cell Press
external identifiers
  • wos:000343682700016
  • pmid:25418171
  • scopus:84908231015
ISSN
1542-0086
DOI
10.1016/j.bpj.2014.08.030
language
English
LU publication?
yes
id
4b078246-b01e-486b-9446-eef8be37a00d (old id 4780778)
date added to LUP
2014-11-20 09:30:42
date last changed
2017-02-05 03:21:03
@article{4b078246-b01e-486b-9446-eef8be37a00d,
  abstract     = {Emphysema and liver cirrhosis can be caused by the Z mutation (Glu342Lys) in the serine protease inhibitor alpha 1-antitrypsin (alpha 1AT), which is found in more than 4% of the Northern European population. Homozygotes experience deficiency in the lung concomitantly with a massive accumulation of polymers within hepatocytes, causing their destruction. Recently, it was proposed that Z-alpha 1AT polymerizes by a C-terminal domain swap. In this study, small-angle x-ray scattering (SAXS) was used to characterize Z-alpha 1AT polymers in solution. The data show that the Z-alpha 1AT trimer, tetramer, and pentamer all form ring-like structures in strong support of a common domain-swap polymerization mechanism that can lead to self-terminating polymers.},
  author       = {Behrens, Manja and Sendall, Timothy J. and Pedersen, Jan S. and Kjeldgaard, Morten and Huntington, James A. and Jensen, Jan K.},
  issn         = {1542-0086},
  language     = {eng},
  number       = {8},
  pages        = {1905--1912},
  publisher    = {Cell Press},
  series       = {Biophysical Journal},
  title        = {The Shapes of Z-alpha(1)-Antitrypsin Polymers in Solution Support the C-Terminal Domain-Swap Mechanism of Polymerization},
  url          = {http://dx.doi.org/10.1016/j.bpj.2014.08.030},
  volume       = {107},
  year         = {2014},
}