Relationship between propeptide pH unfolding and inhibitory ability during ProDer p 1 activation mechanism

[en] The major allergen Der p1 of the house dust mite Dermatophagoides pteronyssinus is a papain-like cysteine protease (CA1) produced as an inactive precursor and associated with allergic diseases. The propeptide of Der p I exhibits a specific fold that makes it unique in the CA1 propeptide family. In this study, we investigated the activation steps involved in the maturation of the recombinant protease Der p 1 expressed in Pichia pastoris and the interaction of the full-length and truncated soluble propepticles with their parent enzyme in terms of activity inhibition and BIAcore interaction analysis. According to our results, the activation of protease Der p 1 is a multistep mechanism that is characterized by at least two intermediates. The propeptide strongly inhibits unglycosylated and glycosylated recombinant Der p 1 (K-D = 7 nM) at neutral pH. This inhibition is pH dependent. It decreases from pH 7 to pH 4 and can be related to conformational changes of the propepticle characterized by an increase of its flexibility and formation of a molten globule state. Our results indicate that activation of the zymogen at pH 4 is a compromise between activity preservation and propeptide unfolding. (c) 2007 Elsevier Ltd. All rights reserved.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Chevigné, Andy ; Université de Liège - ULiège > Macromolécules biologiques

Barumandzadeh, Roya ; Université de Liège - ULiège > Département des sciences de la vie > Laboratoire d'Enzymologie et Repliement des Protéines, Centre d'Ingénierie des Protéines

Groslambert, Sylvie ; Université de Liège - ULiège > Department of Chemical Engineering > PEPs (Product, Environment, Processes)

Cloes, Benoït

Dehareng, Dominique ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Filée, Patrice ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Marx, Jean-Claude

Frère, Jean-Marie ; Université de Liège - ULiège > Département des sciences de la vie > Département des sciences de la vie

Matagne, André ; Université de Liège - ULiège > Département des sciences de la vie > Laboratoire d'Enzymologie et Repliement des Protéines, Centre d'Ingénierie des Protéines

Jacquet, Aurélie ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique

Galleni, Moreno ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques

Language :

English

Title :

Relationship between propeptide pH unfolding and inhibitory ability during ProDer p 1 activation mechanism

Publication date :

16 November 2007

Journal title :

Journal of Molecular Biology

ISSN :

0022-2836

eISSN :

1089-8638

Publisher :

Academic Press Ltd Elsevier Science Ltd, London, United Kingdom

Volume :

374

Issue :

Pages :

170-185

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique
FRFC - Fonds de la Recherche Fondamentale Collective
BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique
DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie

Available on ORBi :

since 05 January 2009

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