Non‐ribosomal insights into ribosomal P2 protein in <i>Plasmodium falciparum</i>‐infected erythrocytes

S, Das; Roy, Bhaskar; Chakrabarty, Saswata

doi:10.1002/mbo3.1188

Cited by 3 publications

(15 citation statements)

References 77 publications

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“…PfP2 tetramer behaves as compared to inherent rec. PfP2 tetramer and whether it shows DTT/beta- ME resistance like PfP2 tetramer in iRBCs ghost (11,12) was a thrilling question to address. When rec.…”

Section: Resultsmentioning

confidence: 99%

“…At the beginning of karyokinesis, at the di-nuclear stage, PfP2 was found to be localized on the iRBC surface as a denaturation resistant tetramer (11,12) . The timing of PfP2 tetramer localization on the iRBC surface and the initiation of nuclear division hinted at the concomitant nature of these two cell biological phenomena during intraerythrocytic karyokinesis.…”

Section: Discussionmentioning

confidence: 99%

“…On the iRBCs surface, PfP2 tetramer exists as a denaturation resistant complex which did not resolve to a monomer even after boiling in DTT treated SDS-PAGE (11)(12)(13). It was difficult to acquire sufficiently pure iRBC ghost tetrameric PfP2 material required for subsequent biochemical and biophysical experimentations to fish out the reasons for denaturation resistance.…”

Section: Synthesis Of Denaturation Resistant Irbc Ghost Pfp2 Tetramermentioning

confidence: 99%

“…In addition, other PEXEL and non-PEXEL proteins have been reported to translocate to the iRBC surface which renders the iRBC membrane more promiscuous and nonselective to solutes and other macromolecules towards the trophozoite stage and schizogony (26)(27). Strangely, 60S stalk ribosomal protein P2, being a non-PEXEL protein has been reported to be present on the iRBC surface during the mid-late trophozoite stage (11)(12)(13). Post-merozoite invasion (PMI) at around 30 hrs, P. falciparum P2 (PfP2) was found to be present on the iRBC surface only for 3-4 hrs, that to as a DTT/β-ME, SDS, and boiling resistant tetramer (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…Strangely, 60S stalk ribosomal protein P2, being a non-PEXEL protein has been reported to be present on the iRBC surface during the mid-late trophozoite stage (11)(12)(13). Post-merozoite invasion (PMI) at around 30 hrs, P. falciparum P2 (PfP2) was found to be present on the iRBC surface only for 3-4 hrs, that to as a DTT/β-ME, SDS, and boiling resistant tetramer (11)(12)(13). When iRBC surface PfP2 was made unaccessible to its bonafide ligand(s) through monoclonal antibody binding, karyokinesis of Plasmodium was arrested at the di-nucleated trophozoite stage at the very beginning of nuclear division 11 .…”

Section: Introductionmentioning

confidence: 99%

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Denaturation resistant P2 tetramer is required to import fatty acids into intraerythrocytic Plasmodium falciparum

Majumder

Bhattacharjya

et al. 2022

Preprint

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The initiation of asymmetric karyokinesis of intraerythrocytic Plasmodium falciparum (Pf) begins with- out dismantling the nuclear envelope showing the hallmark feature of closed mitosis (1-10). In Pf, karyokinesis precedes cytokinesis and cell body formation (6, 8-10). Regulation at the beginning of nu- clear division either through checkpoints or by importing serum components was largely unknown. At the trophozoite stage, PfP2 tetramer trafficked to the infected erythrocyte (IE) surface and the inacces- sibility of IE surface PfP2 to its bonafide ligand led to the arrest of nuclear division (11-13). Here we show that PfP2 tetramer localization on the IE surface and the beginning of nuclear division are con- comitant in nature. Synthetically induced denaturation resistant PfP2 tetramer interacts with human serum fatty acids and phospholipids for its import into IEs at the beginning of karyokinesis. In the na- tively folded denaturation resistant PfP2 tetramer cage, the Cys-Cys redox switch regulates the bind- ing and subsequent release of fatty acids on the IE surface. This mechanistic insight of fatty acids im- port inside IEs using synthetically induced denaturation resistant PfP2 tetramer provides an unique drug screening platform for novel small molecule screening against malaria.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Synthesis Of Denaturation Resistant Irbc Ghost Pfp2 Tetramermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Denaturation resistant P2 tetramer is required to import fatty acids into intraerythrocytic Plasmodium falciparum

Majumder

Bhattacharjya

et al. 2022

Preprint

Self Cite

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M-O-M mediated denaturation resistant P2 tetramer on the infected erythrocyte surface of malaria parasite imports serum fatty acids

Das,

Manna,

Majumdar

et al. 2024

iScience

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Chloroquine induces eryptosis inP. falciparum-infectedred blood cells and the release of extracellular vesicles with a unique protein profile

Carrera-Bravo

Zhou

Hang

et al. 2023

Preprint

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Malaria is a vector-borne parasitic disease that affects millions worldwide. In order to reach the objective, set by the World Health Organization to decrease the cases by 2030, antimalarial drugs with novel modes of action are required. Previously, a novel mechanism of action of chloroquine (CQ) was reported involving features of programmed cell death in the parasite, mainly characterized by calcium efflux from the digestive vacuole (DV) permeabilization. Increased intracellular calcium induces the suicidal death of erythrocytes also known as eryptosis. This study aimed to identify the hallmarks of eryptosis due to calcium redistribution and the downstream cellular effects during CQ treatment in iRBCs. Plasmodium falciparum 3D7 at mid-late trophozoites were used for the antimalarial drug treatment. Our results revealed increased phosphatidylserine (PS) exposure, cell shrinkage and membrane blebbing, delineating an eryptotic phenotype in the host RBC. Interestingly, the blebs on the surface of the iRBCs released to the extracellular milieu become extracellular vesicles (EVs) which are essential for intercellular communication due to their cargo of proteins, nucleic acids, lipids and metabolites. The proteomic characterization displayed 2 highly enriched protein clusters in EVs from CQ-treated iRBCs, the proteasome and ribosome. We demonstrated that this unique protein cargo is not associated with the parasite growth rate. Additionally, we found that these particular EVs might activate IFN signaling pathways mediated by IL-6 in THP-1-derived macrophages. Our findings shed new insights into a novel drug-induced cell death mechanism that targets the parasite and specific components of the infected host RBC.

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Non‐ribosomal insights into ribosomal P2 protein in Plasmodium falciparum‐infected erythrocytes

Cited by 3 publications

References 77 publications

Denaturation resistant P2 tetramer is required to import fatty acids into intraerythrocytic Plasmodium falciparum

Denaturation resistant P2 tetramer is required to import fatty acids into intraerythrocytic Plasmodium falciparum

M-O-M mediated denaturation resistant P2 tetramer on the infected erythrocyte surface of malaria parasite imports serum fatty acids

Chloroquine induces eryptosis inP. falciparum-infectedred blood cells and the release of extracellular vesicles with a unique protein profile

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