title: Human erythroid spectrin alpha subunit and its SH3 domain are sensitive to acidic Plasmodium falciparum proteolytic activity.
abstract: Many proteases play a crucial role in the Plasmodium intraerythrocytic life cycle. Spectrin depletion, one of the major events involved in parasite release from the red blood cell, results from proteolytic activities associated with the presence of the intracellular parasite. Here, we describe a new acidic proteolytic activity from Plasmodium falciparum, whose target is the alpha-subunit of human spectrin. Immunoblotting experiments with antibodies specific for the tryptic peptides of the alpha-chain and in vitro proteolysis tests on recombinant peptides from different regions of the spectrin alpha subunit demonstrated that cleavage sites for the parasite proteolytic activity were localized within the SH3 motif of the alpha-chain sequence. Remarkably, this Plasmodium protease activity on spectrin SH3 substrate was unable to cleave the SH3 from fodrin, a non-erythroid spectrin.
authors.affiliation: Laboratoire de biologie parasitaire et chimiothérapie, ERS CNRS 156, Paris, France.
authors.forename: S L
authors.initials: SL
authors.lastname: Le Bonniec
authors.forename: C
authors.initials: C
authors.lastname: Fournier
authors.forename: C
authors.initials: C
authors.lastname: Deregnaucourt
authors.forename: P
authors.initials: P
authors.lastname: Grellier
authors.forename: D
authors.initials: D
authors.lastname: Dhermy
authors.forename: M C
authors.initials: MC
authors.lastname: Lecomte
authors.forename: J
authors.initials: J
authors.lastname: Schrevel
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007460:Iodoacetamide / Q000494:pharmacology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010436:Pepstatins / Q000494:pharmacology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000201:enzymology*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013049:Spectrin / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics; D018909:src Homology Domains / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D007460:Iodoacetamide; D008840:Microfilament Proteins; D010436:Pepstatins; D010664:Phenylmethylsulfonyl Fluoride; D011480:Protease Inhibitors; D013049:Spectrin