Plasmodium falciparum: Isolation and characterization of a 55-kDa protease with a cathepsin D-like activity from P. falciparum

Bailly, Éric; Savel, J; Mahouy, G.; Jaureguiberry, Ginette

doi:10.1016/0014-4894(91)90147-o

Cited by 19 publications

(9 citation statements)

References 21 publications

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“…Involvement of aspartic proteases in hemoglobin digestion was suspected nearly 50 years ago from the characterization of crude parasite extracts (25,26). The older literature contains numerous reports of hemoglobin-degrading acidic protease activities in various Plasmodium species, and some were shown to be blocked by the canonical aspartic protease inhibitor pepstatin A (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Their cellular roles remained unclear until studies on isolated digestive vacuoles showed the ability to degrade hemoglobin (16,35), and protease inhibitor profiling of hemoglobinase activity from highly purified digestive vacuoles revealed a central role for aspartic proteases (16).…”

Section: Discoverymentioning

confidence: 99%

“…These plasmepsins are capable of forming dimers in crystalline form and in solution (69,70), although it is the monomer that has been shown to be active. The PM III dimer has a loop from one of the subunits that intrudes into the second subunit active site, where it coordinates a zinc ion via Asp 215 and His 32 (67). The canonical Asp 215 -Thr 218 hydrogen bond is disrupted by the zinc coordination.…”

Section: Structure and Mechanismmentioning

confidence: 99%

“…We suggest going back to a convention initiated in early publications of having Roman numerals after a space. We further suggest that HAP be referred to as PM III for consis-tency with the other plasmepsins and because its His 32 has not been shown to be catalytic. Also, HAP is the name for a gamete fusion protein.…”

mentioning

confidence: 91%

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Malaria parasite plasmepsins: More than just plain old degradative pepsins

Nasamu¹,

Polino²,

Istvan

et al. 2020

Journal of Biological Chemistry

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Plasmepsins are a group of diverse aspartic proteases in the malaria parasite Plasmodium. Their functions are strikingly multifaceted, ranging from hemoglobin degradation to secretory organelle protein processing for egress, invasion, and effector export. Some, particularly the digestive vacuole plasmepsins, have been extensively characterized, whereas others, such as the transmission-stage plasmepsins, are minimally understood. Some (e.g. plasmepsin V) have exquisite cleavage sequence specificity; others are fairly promiscuous. Some have canonical pepsin-like aspartic protease features, whereas others have unusual attributes, including the nepenthesin loop of plasmepsin V and a histidine in place of a catalytic aspartate in plasmepsin III. We have learned much about the functioning of these enzymes, but more remains to be discovered about their cellular roles and even their mechanisms of action. Their importance in many key aspects of parasite biology makes them intriguing targets for antimalarial chemotherapy. Further consideration of their characteristics suggests that some are more viable drug targets than others. Indeed, inhibitors of invasion and egress offer hope for a desperately needed new drug to combat this nefarious organism.

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Section: Discoverymentioning

confidence: 99%

Section: Structure and Mechanismmentioning

confidence: 99%

See 1 more Smart Citation

Malaria parasite plasmepsins: More than just plain old degradative pepsins

Nasamu¹,

Polino²,

Istvan

et al. 2020

Journal of Biological Chemistry

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“…The following antibodies were used: mAb W6/32 (Barnstable et al, 1978), recognizing properly folded human class I complexes; mAb HC10 , specific for human class I free heavy chains (HCs); antihuman HC serum (Stam et al, 1986), specific for free human HCs; antimouse HC serum (Machold et al, 1995), recognizing free HCs only; anti-p8 serum (raised in our laboratory, according to Smith et al [1986], against a synthetic peptide representing the most COOH-terminal exon of the H-2K b molecule); anti-human 132m serum (raised against highly purified [~2 m, separated from HLA-A2 and HLA-A28 by gel filtration in acetic acid); rabbit anti-ER serum provided by Dr. D. Louvard (Institut Pasteur, Paris, France) (Louvard et al, 1982); mouse monoclonal anti-PDI (ID3) provided by Dr. S. Fuller (EMBL, Heidelberg, Germany) (Vaux et al, 1990); rabbit anti-bovine cathepsin D provided by Dr. G. Jaureguiberry (IN-SERM U.13, Hopital Claude Bernard, Paris, France) (Bailly et al, 1991); mouse monoclonal anti-ERGIC 53 provided by Dr. H. P. Hauri (University of Basel, Basel, Switzerland) (Schweizer et al, 1988); rabbit polyclonal affinity purified anti-human ubiquitin and mouse monoclonal anti-E1 provided by Dr. A. Schwartz (Washington University, St. Louis, MO) (Schwartz et al, , 1992. To visualize the primary antibodies nondirectly reactive with protein A, rabbit anti-mouse IgG and rabbit antimouse IgM (Nordic Immunochemicals, Tilburg, The Netherlands) were used.…”

Section: Antibodiesmentioning

confidence: 99%

Misfolded major histocompatibility complex class I molecules accumulate in an expanded ER-Golgi intermediate compartment.

Raposo

Santen

Leijendekker

et al. 1995

The Journal of Cell Biology

127

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Abstract. Misfolded membrane proteins are rapidly degraded, often shortly after their synthesis and insertion in the endoplasmic reticulum (ER), but the exact location and mechanisms of breakdown remain unclear. We have exploited the requirement of MHC class I molecules for peptide to achieve their correct conformation: peptide can be withheld by introducing a null mutation for the MHC-encoded peptide transporter, TAP. By withholding TAP-dependent peptides, the vast majority of newly synthesized class I molecules fails to leave the endoplasmic reticulum and is degraded. We used mice transgenic for HLA-B27 on a TAPl-deficient background to allow visualization by immunoelectron microscopy of misfolded HLA-B27 molecules in thymic epithelial cells. In such HLA transgenic animals, the TAP mutation can be considered a genetic switch that allows control over the extent of folding of the protein of interest, HLA-B27, while the rate of synthesis of the constituent subunits remains unaltered.,In TAPl-deficient, HLA-B27 transgenic animals, HLA-B27 molecules fail to assemble correctly, and do not undergo carbohydrate modifications associated with the Golgi apparatus, such as conversion to Endoglycosidase H resistance, and acquisition of sialic acids. We show that such molecules accumulate in an expanded network of tubular and fenestrated membranes. This compartment has its counterpart in normal thymic epithelial cells, and is identified as an ER-Golgi intermediate. We detect the presence of ubiquitin and ubiquitin-conjugating enzymes in association with this compartment, suggesting a nonlysosomal mode of degradation of its contents.

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“…Tu 30 was raised against the Myr 1 amino terminus, and Tu 22 was raised against a synthetic peptide of the Myr 1 tail (Ruppert et al, 1993). We also used polyclonal antibodies directed against rab 5 (Chavrier et al, 1990), polyclonal antibodies directed against the cytoplasmic tail of the lysosomal membrane glycoprotein (lgp 120) (Bakker et al, 1997), monoclonal antibody directed against the Golgi complex (Jasmin et al, 1989), monoclonal antibody directed against rab 7 (Meresse et al, 1995), polyclonal antibodies directed against cathepsin D (Bailly et al, 1991), and monoclonal antibody H68.4 directed against the cytoplasmic tail of transferrin receptor according to White et al (1992). Polyclonal antibodies directed against ␤-actin were a generous gift from C. Chaponnier (Geneva University, Geneva, Switzerland).…”

Section: Antibodiesmentioning

confidence: 99%

Association of Myosin I Alpha with Endosomes and Lysosomes in Mammalian Cells

Raposo

Cordonnier

Tenza

et al. 1999

MBoC

111

106

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Myosin Is, which constitute a ubiquitous monomeric subclass of myosins with actinbased motor properties, are associated with plasma membrane and intracellular vesicles. Myosin Is have been proposed as key players for membrane trafficking in endocytosis or exocytosis. In the present paper we provide biochemical and immunoelectron microscopic evidence indicating that a pool of myosin I alpha (MMI␣) is associated with endosomes and lysosomes. We show that the overproduction of MMI␣ or the production of nonfunctional truncated MMI␣ affects the distribution of the endocytic compartments. We also show that truncated brush border myosin I proteins, myosin Is that share 78% homology with MMI␣, promote the dissociation of MMI␣ from vesicular membranes derived from endocytic compartments. The analysis at the ultrastructural level of cells producing these brush border myosin I truncated proteins shows that the delivery of the fluid phase markers from endosomes to lysosomes is impaired. MMI␣ might therefore be involved in membrane trafficking occurring between endosomes and lysosomes.

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Plasmodium falciparum: Isolation and characterization of a 55-kDa protease with a cathepsin D-like activity from P. falciparum

Cited by 19 publications

References 21 publications

Malaria parasite plasmepsins: More than just plain old degradative pepsins

Malaria parasite plasmepsins: More than just plain old degradative pepsins

Misfolded major histocompatibility complex class I molecules accumulate in an expanded ER-Golgi intermediate compartment.

Association of Myosin I Alpha with Endosomes and Lysosomes in Mammalian Cells

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