[HTML][HTML] Molecular mechanism of Z α1-antitrypsin deficiency
X Huang, Y Zheng, F Zhang, Z Wei, Y Wang… - Journal of Biological …, 2016 - ASBMB
The Z mutation (E342K) of α1-antitrypsin (α1-AT), carried by 4% of Northern Europeans,
predisposes to early onset of emphysema due to decreased functional α1-AT in the lung and
to liver cirrhosis due to accumulation of polymers in hepatocytes. However, it remains
unclear why the Z mutation causes intracellular polymerization of nascent Z α1-AT and why
15% of the expressed Z α1-AT is secreted into circulation as functional, but polymerogenic,
monomers. Here, we solve the crystal structure of the Z-monomer and have engineered …
predisposes to early onset of emphysema due to decreased functional α1-AT in the lung and
to liver cirrhosis due to accumulation of polymers in hepatocytes. However, it remains
unclear why the Z mutation causes intracellular polymerization of nascent Z α1-AT and why
15% of the expressed Z α1-AT is secreted into circulation as functional, but polymerogenic,
monomers. Here, we solve the crystal structure of the Z-monomer and have engineered …