IMR Press / FBL / Volume 10 / Issue 1 / DOI: 10.2741/1528

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

A protein family under 'stress' – serpin stability, folding and misfolding

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1 Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia

Academic Editor: Philip Patston

Front. Biosci. (Landmark Ed) 2005, 10(1), 288–299; https://doi.org/10.2741/1528
Published: 1 January 2005
(This article belongs to the Special Issue Serpins in biology and medicine)
Abstract

The native fold of inhibitory serpins (serpin proteinase inhibitors) is metastable and therefore does not represent the most stable conformation that the primary sequence encodes for. The most stable form is adopted when the reactive centre loop (RCL) inserts, as the fourth strand, into the A β-sheet. Currently a serpin can adopt at least four more stable conformations, termed the cleaved, delta, latent and polymeric states. The accessibility of these alternative low energy folds renders the serpin molecule susceptible to mutations that can result in dysfunction and pathology. Here, we discuss the means by which the serpin can attain and preserve this metastable conformation. We also consider the triggers for misfolding to these more stable states and the mechanisms by which it occurs.

Keywords
Serpin
Protein misfolding
Protein folding
Protein aggregation
Conformational disease
Review
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