Alpha 1-antitrypsin polymerisation can occur by both loop A and C sheet mechanisms.
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.
Bottomley
S P
SP
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3168, Australia. steve.bottomley@med.monash.edu.au
Hopkins
P C
PC
Whisstock
J C
JC
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*
D011108:Polymers; D015843:Serpins; D000515:alpha 1-Antitrypsin