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Mini-Review
Protein Misfolding and the Serpinopathies
Didier Belorgey, Peter Hägglöf, Susanna Karlsson-Li and David A. Lomas
volume 1 | issue 1
January/February/March 2007We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
The serpins are the largest superfamily of protease inhibitors. They are found in almost all branches of life including viruses, prokaryotes and eukaryotes. They inhibit their target protease by a unique mechanism that involves a large conformational transition and the translocation of the enzyme from the upper to the lower pole of the protein. This complex mechanism, and the involvement of serpins in important biological regulatory processes, make them prone to mutation-related diseases. For example the polymerization of mutant α 1-antitrypsin leads to the accumulation of ordered polymers within the endoplasmic reticulum of hepatocytes in association with cirrhosis. An identical process in the neuron specific serpin, neuroserpin, results in the accumulation of polymers in neurons and the dementia FENIB. In both cases there is a clear correlation between the molecular instability, the rate of polymer formation and the severity of disease. A similar process underlies the hepatic retention and plasma deficiency of antithrombin, C1 inhibitor, α 1-antichymotrypsin and heparin co-factor II. The common mechanism of polymerization has allowed us to group these conditions together as a novel class of disease, the serpinopathies.
Authors
Didier Belorgey
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Peter Hägglöf
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Susanna Karlsson-Li
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
David A. Lomas
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.