title: Cleaved antitrypsin polymers at atomic resolution.
abstract: 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.
authors.affiliation: The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Dunstone
authors.forename: W
authors.initials: W
authors.lastname: Dai
authors.forename: J C
authors.initials: JC
authors.lastname: Whisstock
authors.forename: J
authors.initials: J
authors.lastname: Rossjohn
authors.forename: R N
authors.initials: RN
authors.lastname: Pike
authors.forename: S C
authors.initials: SC
authors.lastname: Feil
authors.forename: B F
authors.initials: BF
authors.lastname: Le Bonniec
authors.forename: M W
authors.initials: MW
authors.lastname: Parker
authors.forename: S P
authors.initials: SP
authors.lastname: Bottomley
mesh_terms: 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
chemical_list: D001704:Biopolymers; D000515:alpha 1-Antitrypsin