Der p 1 is the primary activator of Der p 3, Der p 6 and Der p 9 the proteolytic allergens produced by the house dust mite Dermatophagoides pteronyssinus
[en] Background: The enzymatic activity of the four proteases found in the house dust mite Dermatophagoides
pteronyssinus is involved in the pathogenesis of allergy. Our aim was to elucidate the activation cascade of
their corresponding precursor forms and particularly to highlight the interconnection between proteases during
this cascade.
Methods: The cleavage of the four peptides corresponding to the mite zymogen activation sites was studied on
the basis of the Förster Resonance Energy Transfermethod. The proDer p 6 zymogen was then produced in Pichia
pastoris to elucidate its activation mechanismbymite proteases, especially Der p 1. The role of the propeptide in
the inhibition of the enzymatic activity of Der p 6 was also examined. Finally, the Der p 1 and Der p 6 proteases
were localised via immunolocalisation in D. pteronyssinus.
Results: All peptides were specifically cleaved by Der p 1, such as proDer p 6. The propeptide of proDer p 6
inhibited the proteolytic activity of Der p 6, but once cleaved, it was degraded by the protease. The Der p 1 and
Der p 6 proteases were both localised to the midgut of the mite.
Conclusions: Der p 1 in either its recombinant formor in the natural context of house dustmite extracts specifically
cleaves all zymogens, thus establishing its role as a major activator of both mite cysteine and serine proteases.
General significance: This finding suggests that Der p 1 may be valuable target against mites.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Herman, Julie ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Thelen, Nicolas ; Université de Liège - ULiège > Département des sciences de la vie > Biologie cellulaire
Smargiasso, Nicolas ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)
Mailleux, Anne-Catherine; Université catholique de Louvain - UCL > Earth and Life Institute
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
Cloes, Marie ; Université de Liège - ULiège > Département des sciences de la vie > Biologie cellulaire
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)
Chevigné, Andy; CRP-Santé, Luxembourg > Laboratory of Retrovirology
Galleni, Moreno ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Dumez, Marie-Eve ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Language :
English
Title :
Der p 1 is the primary activator of Der p 3, Der p 6 and Der p 9 the proteolytic allergens produced by the house dust mite Dermatophagoides pteronyssinus
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