Plasmodium falciparum Merozoite Surface Protein 3

Imam, Maryam; Singh, Shailja; Kaushik, Neeraj; Chauhan, Virander S.

doi:10.1074/jbc.m113.520239

Cited by 25 publications

(12 citation statements)

References 73 publications

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“…Another finding of the present study is that the MSP3 N-terminal region (aa 21 to 238) is mainly involved in the interaction with PfMSP1. These results are in line with previous reports suggesting that MSP3 exists in a complex as an elongated dimer/tetramer on the merozoite surface and that its coiled-coil domain-adherent structure that is represented by its N-terminal domain is mainly involved in formation of various large complexes with other proteins on the merozoite surface (12,16,19,26). The long, extended fibrillary nature of the MSP3 molecule complexed with other GPI-anchored or non-GPI-anchored merozoite surface proteins thus allows flexibility of the merozoite complex of proteins to trap or reach the ligands of the erythrocytes (5,8,24,31,(35)(36)(37)(38).…”

Section: Discussionsupporting

confidence: 93%

“…Indirect immunofluorescent assay. Indirect immunofluorescence assays were performed on the merozoite stage of P. falciparum 3D7 parasites as described earlier (12,26,28,40). Parasite smears on the glass slide were fixed using prechilled methanol-acetone for 20 min and allowed to air dry at room temperature (RT).…”

Section: Methodsmentioning

confidence: 99%

“…A number of MSPs, such as MSP1, MSP4, MSP5, and MSP10, are anchored to the merozoite membrane (11,12), while others, such as MSP6, MSP7, and MSP9, are attached to the merozoite surface through protein-protein interactions (13)(14)(15). Some of these MSPs bind human erythrocytes and play a role in the invasion of red cells (9,16).…”

mentioning

confidence: 99%

“…These polymorphisms define two major allele types, K1 and 3D7 (22). Biophysical studies suggest that the full-length MSP3 forms elongated oligomeric structures through protein-protein interactions between residues in the C-terminal region (12,19,23). Studies performed on long, synthetic peptides from the oligomeric region suggested that the C-terminal residues may be involved in erythrocyte binding activity.…”

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confidence: 99%

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Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

et al. 2018

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merozoite surface protein 3 (MSP3) is an abundantly expressed secreted merozoite surface protein and a leading malaria vaccine candidate antigen. However, it is unclear how MSP3 is retained on the surface of merozoites without a glycosylphosphatidylinositol (GPI) anchor or a transmembrane domain. In the present study, we identified an MSP3-associated network on the merozoite surface by immunoprecipitation of merozoite lysate using antibody to the N terminus of MSP3 (anti-MSP3N) followed by mass spectrometry analysis. The results suggested the association of MSP3 with other merozoite surface proteins: MSP1, MSP6, MSP7, RAP2, and SERA5. Protein-protein interaction studies by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analysis showed that MSP3 complex consists of MSP1, MSP6, and MSP7 proteins. Immunological characterization of MSP3 revealed that MSP3N is strongly recognized by hyperimmune serum from African and Asian populations. Furthermore, we demonstrate that human antibodies, affinity purified against recombinant MSP3N (rMSP3N), promote opsonic phagocytosis of merozoites in cooperation with monocytes. At nonphysiological concentrations, anti-MSP3N antibodies inhibited the growth of Together, the data suggest that MSP3 and especially its N-terminal region containing known B/T cell epitopes are targets of naturally acquired immunity against malaria and also comprise an important candidate for a multisubunit malaria vaccine.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

et al. 2018

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“…DLS experiments were performed using a Malvern Zetasizer Nano ZS instrument (Malvern, Worcestershire, UK) at 25°C, as described previously 44 . Freshly purified PKD2L1 CT and deletion mutants from E. coli in a solution containing 50 mM NaH 2 PO4, 300 mM NaCl and 250 mM imidazole, pH 8.0 were passed through a 0.22 μm filter to remove large particles or aggregates and diluted to 0.4 mg/ml before measurements.…”

Section: Methodsmentioning

confidence: 99%

A novel PKD2L1 C-terminal domain critical for trimerization and channel function

Zheng

Hussein

Yang

et al. 2015

Sci Rep

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As a transient receptor potential (TRP) superfamily member, polycystic kidney disease 2-like-1 (PKD2L1) is also called TRPP3 and has similar membrane topology as voltage-gated cation channels. PKD2L1 is involved in hedgehog signaling, intestinal development, and sour tasting. PKD2L1 and PKD1L3 form heterotetramers with 3:1 stoichiometry. C-terminal coiled-coil-2 (CC2) domain (G699-W743) of PKD2L1 was reported to be important for its trimerization but independent studies showed that CC2 does not affect PKD2L1 channel function. It thus remains unclear how PKD2L1 proteins oligomerize into a functional channel. By SDS-PAGE, blue native PAGE and mutagenesis we here identified a novel C-terminal domain called C1 (K575-T622) involved in stronger homotrimerization than the non-overlapping CC2, and found that the PKD2L1 N-terminus is critical for dimerization. By electrophysiology and Xenopus oocyte expression, we found that C1, but not CC2, is critical for PKD2L1 channel function. Our co-immunoprecipitation and dynamic light scattering experiments further supported involvement of C1 in trimerization. Further, C1 acted as a blocking peptide that inhibits PKD2L1 trimerization as well as PKD2L1 and PKD2L1/PKD1L3 channel function. Thus, our study identified C1 as the first PKD2L1 domain essential for both PKD2L1 trimerization and channel function, and suggest that PKD2L1 and PKD2L1/PKD1L3 channels share the PKD2L1 trimerization process.

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Mycobacterium tuberculosis low molecular weight T‐cell antigen Mtb8.4 has heme‐binding and fiber‐forming properties

et al. 2022

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Mtb8.4, a secretory T‐cell antigen of Mycobacterium tuberculosis, is important for providing an antigen‐specific immune response. In this study, we showed Mtb8.4 to have both heme‐binding and fibril‐forming properties, using experimental and in silico methods. High absorbance at 410 nm and interaction with hemin‐agarose demonstrated its heme‐binding nature. Titration of Mtb8.4 with heme resulted in 1 : 1 stoichiometry. The heme‐binding pocket in Mtb8.4 was identified by molecular modeling, and binding residues were predicted using molecular docking. The molecular dynamics simulations of apo‐ and heme‐bound Mtb8.4 confirmed that the heme group forms a stable complex. Transmission electron microscopy analyses and dye‐binding assays showed that Mtb8.4 forms fibers. Computational studies predicted that the C‐terminal sequence (93AAQYIGLVESV103) is important for forming fibers. In silico analyses further anticipated the probable epitope (82AMAAQLQAV90) of Mtb8.4. The fiber‐forming properties of Mtb8.4 could be advantageous from a vaccine perspective for aggregate/fibril‐based vaccine delivery or it might influence the epitope presentation of Mtb8.4.

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Plasmodium falciparum Merozoite Surface Protein 3

Cited by 25 publications

References 73 publications

Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

A novel PKD2L1 C-terminal domain critical for trimerization and channel function

Mycobacterium tuberculosis low molecular weight T‐cell antigen Mtb8.4 has heme‐binding and fiber‐forming properties

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