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Nucleation of alpha1-Antichymotrypsin Polymerization
journal contribution
posted on 2023-06-07, 20:38 authored by Damian C Crowther, Louise SerpellLouise Serpell, Timothy R Daffron, Bibek Gooptu, David A LomasAlpha(1)-antichymotrypsin is an acute phase plasma protein and a member of the serpin superfamily. We show here that wildtype alpha(1)-antichymotrypsin forms polymers between the reactive center loop of one molecule and the beta-sheet A of a second at a rate that is dependent on protein concentration and the temperature of the reaction. The rate of polymerization was accelerated by seeding with polymers of alpha(1)-antichymotrypsin and a complex of alpha(1)-antichymotrypsin with an exogenous reactive loop peptide but not with reactive loop cleaved alpha(1)-antichymotrypsin or with polymers of other members of the serpin superfamily. Sonication of alpha(1)-antichymotrypsin polymers markedly increased the efficacy of seeding such that polymers were able to form under physiological conditions. Taken together, these data provide the first demonstration that serpin polymerization can result from seeding. This mechanism is analogous to the fibrillization of the Abeta(1-42) peptide and may be important in the deposition of alpha(1)-antichymotrypsin in the plaques of Alzheimer's disease.
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Publication status
- Published
Journal
BiochemistryISSN
0006-2960External DOI
Issue
8Volume
42Page range
2355-2363Department affiliated with
- Biochemistry Publications
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- No
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- Yes
Legacy Posted Date
2012-02-06Usage metrics
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