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Cleaved antitrypsin polymers at atomic resolution

Published online by Cambridge University Press:  01 February 2000

MICHELLE A. DUNSTONE ,
WEIWEN DAI ,
JAMES C. WHISSTOCK ,
JAMIE ROSSJOHN ,
ROBERT N. PIKE ,
SUSANNE C. FEIL ,
BERNARD F. LE BONNIEC ,
MICHAEL W. PARKER  and
STEPHEN P. BOTTOMLEY
MICHELLE A. DUNSTONE
Affiliation:
The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
WEIWEN DAI
Affiliation:
The Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, Victoria, 3168 Australia
JAMES C. WHISSTOCK
Affiliation:
The Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, Victoria, 3168 Australia
JAMIE ROSSJOHN
Affiliation:
The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
ROBERT N. PIKE
Affiliation:
The Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, Victoria, 3168 Australia
SUSANNE C. FEIL
Affiliation:
The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
BERNARD F. LE BONNIEC
Affiliation:
INSERM, Unité 428, Université Paris V, 75270 Paris Cedex 06, France
MICHAEL W. PARKER
Affiliation:
The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
STEPHEN P. BOTTOMLEY
Affiliation:
The Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, Victoria, 3168 Australia
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Abstract

α1-Antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of α1-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that α1-antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the β-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 β-strand linked polymer form of α1-antitrypsin: the crystal structure of a cleaved α1-antitrypsin polymer.

Keywords

α1-antitrypsin deficiencyconformational diseasepolymerizationX-ray crystallography
Type
FOR THE RECORD
Information
Protein Science , Volume 9 , Issue 2 , February 2000 , pp. 417 - 420
Copyright
© 2000 The Protein Society

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