Cleaved antitrypsin polymers at atomic resolution.
Alpha1-antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of alpha1-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that alpha1-antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the beta-sheet of another. However, this long-standing hypothesis has not been confirmed by direct structural evidence. Here, we describe the first crystallographic evidence of a beta-strand linked polymer form of alpha1-antitrypsin: the crystal structure of a cleaved alpha1-antitrypsin polymer.
Dunstone
M A
MA
The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Dai
W
W
Whisstock
J C
JC
Rossjohn
J
J
Pike
R N
RN
Feil
S C
SC
Le Bonniec
B F
BF
Parker
M W
MW
Bottomley
S P
SP
D001704:Biopolymers / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D000515:alpha 1-Antitrypsin / Q000737:chemistry*; D019896:alpha 1-Antitrypsin Deficiency / Q000378:metabolism
D001704:Biopolymers; D000515:alpha 1-Antitrypsin