Structural transition of α1‐antitrypsin by a peptide sequentially similar to β‐strand s4A

Abstract

Crystal structure studies have shown that cleaved and intact serpins differ essentially in the topology of β‐sheet A. This is five‐stranded in the intact molecules and six‐stranded after cleavage by insertion of strand s4A whose C‐terminus has become free [Löbermann, H., Tokuoka, R., Deisenhofer, J. & Huber, R. (1984) J. Mol. Biol. 177, 531–556; Wright, T. H., Qian, H. X. & Huber, R. (1990) J. Mol. Biol. 213, 513–528]. The structural transition is accømpanied by changes in spectral properties and an increase in thermal stability. We show here that an Nα‐acetyl‐tetradecapeptide with the amino acid sequence of strand s4A, residues 345–358 of human α1‐antitrypsin, associates with intact α1‐antitrypsin and forms a stoichiometric complex with properties very similar to cleaved α1‐antitrypsin. Complex generation has the characteristics of a folding process. Copyright © 1990, Wiley Blackwell. All rights reserved