Reference : Relationship between propeptide pH unfolding and inhibitory ability during ProDer p 1 ac...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/3523
Relationship between propeptide pH unfolding and inhibitory ability during ProDer p 1 activation mechanism
English
Chevigné, Andy [Université de Liège - ULg > > Macromolécules biologiques >]
Barumandzadeh, Roya mailto [Université de Liège - ULg > Département des sciences de la vie > Laboratoire d'Enzymologie et Repliement des Protéines, Centre d'Ingénierie des Protéines > >]
Groslambert, Sylvie [> > > >]
Cloes, Benoït [> > > >]
Dehareng, Dominique mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Filée, Patrice mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Marx, Jean-Claude [> > > >]
Frère, Jean-Marie mailto [Université de Liège - ULg > Département des sciences de la vie > Département des sciences de la vie >]
Matagne, André mailto [Université de Liège - ULg > Département des sciences de la vie > Laboratoire d'Enzymologie et Repliement des Protéines, Centre d'Ingénierie des Protéines > >]
Jacquet, Aurélie [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
Galleni, Moreno mailto [Université de Liège - ULg > Département des sciences de la vie > Macromolécules biologiques >]
16-Nov-2007
Journal of Molecular Biology
Academic Press Ltd Elsevier Science Ltd
374
1
170-185
Yes (verified by ORBi)
International
0022-2836
1089-8638
London
[en] allergy ; cysteine protease ; inhibition mechanism ; propeptide ; pH unfolding
[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.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Fonds de la Recherche Fondamentale Collective d’Initiative des Chercheurs - FRFC ; Politique Scientifique Fédérale (Belgique) = Belgian Federal Science Policy ; Région wallonne : Direction générale des Technologies, de la Recherche et de l'Energie - DGTRE
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/3523
10.1016/j.jmb.2007.08.025

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