title: Alpha 1-antitrypsin polymerisation can occur by both loop A and C sheet mechanisms.
abstract: A number of disease states are attributable to alpha1-antitrypsin polymerisation within the endoplasmic reticulum of hepatocytes and subsequent plasma deficiency. Two distinct mechanisms describing the process of alpha1-antitrypsin polymerisation have been proposed, the loop A-sheet and C-sheet mechanisms. We report fluorescence studies using alpha1-antitrypsin covalently modified with pyrene maleimide. These results in conjunction with detailed molecular modelling studies, show that alpha1-antitrypsin is capable of undergoing both loop A-sheet and loop C-sheet mechanisms of polymerisation, depending upon the in vitro buffer conditions.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3168, Australia. steve.bottomley@med.monash.edu.au
authors.forename: S P
authors.initials: SP
authors.lastname: Bottomley
authors.forename: P C
authors.initials: PC
authors.lastname: Hopkins
authors.forename: J C
authors.initials: JC
authors.lastname: Whisstock
mesh_terms: D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D015843:Serpins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D000515:alpha 1-Antitrypsin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011108:Polymers; D015843:Serpins; D000515:alpha 1-Antitrypsin