TY - JOUR
T1 - The Shapes of Z-α1-Antitrypsin Polymers in Solution Support the C-Terminal Domain-Swap Mechanism of Polymerization
AU - Behrens, Manja Annette
AU - Sendall, Timothy J.
AU - Pedersen, Jan Skov
AU - Kjeldgaard, Morten
AU - Huntington, James A.
AU - Jensen, Jan Kristian
PY - 2014/10/21
Y1 - 2014/10/21
N2 - Emphysema and liver cirrhosis can be caused by the Z mutation (Glu342Lys) in the serine protease inhibitor α1-antitrypsin (α1AT), 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-α1AT polymerizes by a C-terminal domain swap. In this study, small-angle x-ray scattering (SAXS) was used to characterize Z-α1AT polymers in solution. The data show that the Z-α1AT 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
AB - Emphysema and liver cirrhosis can be caused by the Z mutation (Glu342Lys) in the serine protease inhibitor α1-antitrypsin (α1AT), 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-α1AT polymerizes by a C-terminal domain swap. In this study, small-angle x-ray scattering (SAXS) was used to characterize Z-α1AT polymers in solution. The data show that the Z-α1AT 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
U2 - 10.1016/j.bpj.2014.08.030
DO - 10.1016/j.bpj.2014.08.030
M3 - Journal article
C2 - 25418171
SN - 0006-3495
VL - 107
SP - 1905
EP - 1912
JO - Biophysical Journal
JF - Biophysical Journal
IS - 8
ER -