Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.
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PMID:A malaria merozoite surface protein (MSP1)-structure, processing and function. 134 16

A well conserved 83-kDa apical membrane antigen of Plasmodium falciparum, PF83/AMA-1, is the analogue of PK66/AMA-1, a 66-kDa P. knowlesi protective merozoite protein. PK66/AMA-1 is expressed in late-stage schizonts; is localized within the merozoite apex; and is processed to a 44/42-kDa doublet at, or around, the time of schizont rupture. The processed forms can associate with the merozoite surface. We were interested to further analyze the timing of synthesis and processing, and subcellular localization of PF83/AMA-1, a malaria vaccine candidate, using monoclonal antibodies (mAbs) developed against PF83/AMA-1. Using [35S]methionine metabolically labeled asexual blood stage parasites, in combination with indirect single and dual immunofluorescence, we have determined that, in similar fashion to PK66/AMA-1, protein expression of PF83/AMA-1 is restricted to late-stage schizonts with greater than 8 nuclei. PF83/AMA-1 is post-synthetically processed rapidly by cleavage of an N-terminal peptide to a 66-kDa molecule. Both the 83- and the 66-kDa molecules are initially localized at the merozoite apex. In P. falciparum (7G8 strain and CVD-1 clone) the full-length 83-kDa molecule remains apically restricted following merozoite release. However, the processed 66-kDa form can become circumferentially associated with the merozoite surface at or around the time of schizont rupture and merozoite release. After merozoite invasion a processed form of PF83/AMA-1 is present in early ring stage parasites. Comparative analysis of a rhoptry associated protein RAP-1, shows a co-ordinated and compartmentalized release of rhoptry components.
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PMID:Differential localization of full-length and processed forms of PF83/AMA-1 an apical membrane antigen of Plasmodium falciparum merozoites. 783 84

The mechanism of malaria protective immunity induced by immunization with radiation-attenuated Plasmodium sporozoites (SPZ) is only partially understood. For example, B and T cell responses specific for the circumsporozoite (CS) protein, a 46 kDa SPZ surface protein, have been characterized; however, events leading to SPZ-specific T cell activation, i.e., processing and presentation of SPZ by antigen-presenting cells have not been investigated. In the present study we describe the in vitro analysis of requirements for accessory cell function in the presentation of SPZ to SPZ-immune T cells. The results establish that SPZ-induced proliferative T cells are reactive to non-processed SPZ presented by activated B cells and, thus, imply that the non-processed form of the SPZ-associated CS protein restricts the induction of the potential CS protein T cell repertoire.
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PMID:Plasmodium berghei-specific T cells respond to non-processed sporozoites presented by B cells. 837 Apr 5

The potential of Plasmodium falciparum merozoite surface protein 3 as a component of an asexual-stage malaria vaccine is currently being assessed. The precursor form of MSP3 undergoes cleavage during schizogony to generate a mature processed form. It is unknown if this cleavage event is necessary for MSP3 function, but it may be an important consideration for assessing and developing MSP3 as an asexual-stage vaccine candidate. We have therefore determined the cleavage site in MSP3 by sequencing the N-terminus of the processed form of MSP3, which was isolated from parasite material. The position of the cleavage site indicates that the processed form of MSP3 retains the three blocks of alanine-rich heptad repeats, which are predicted to provide the structural framework for an intramolecular coiled-coil. The cleavage-site motif has many features in common with the published cleavage sites of MSP1(30), MSP6(36), and MSP7(22), which are all located on the merozoite surface and are implicated in the erythrocyte invasion process. The common cellular location and similar cleavage-site motifs suggest that these merozoite proteins may be cleaved by the same or related proteases.
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PMID:The alanine-rich heptad repeats are intact in the processed form of Plasmodium falciparum MSP3. 1558 17

Merozoites of the malaria parasite Plasmodium falciparum expose at their surface a large multiprotein complex, composed of proteolytically processed, noncovalently associated products of at least three genes, msp-1, msp-6, and msp-7. During invasion of erythrocytes, this complex is shed from the surface except for a small glycosylphosphatidylinositol-anchored portion originating from MSP-1. The proteolytic cleavage separating the C-terminal portion of MSP-1 is required for successful invasion. Little is known about the structure and function of the abundant and essential multipartite complex. Using heterologously produced MSP-1, MSP-6, and MSP-7 in precursor and with the exception of MSP-7 in processed form, we have studied in vitro the complex formation between the different proteins to identify the interaction partners within the complex. Both MSP-6(36) and MSP-7 bind only to MSP-1 subunits that are shed, but although MSP-6(36) contacts just subunit p38, MSP-7 interacts with p83, p30, and p38. The intact C-terminal region of MSP-6 is required for the association with p38 as well as for its multimerization into tetramers. Furthermore, our data suggest that only the processed form and not the precursor form of MSP-1 interacts with MSP-6(36). MSP-6- as well as MSP-7-specific rabbit antibodies inhibit parasite multiplication in vitro as shown previously for antibodies directed against MSP-1. Our findings raise interesting questions with regard to proteolysis-mediated mechanisms of maturation of the MSP-1-MSP-6-MSP-7 complex and to the mode by which antibodies directed against this complex interfere with parasite multiplication.
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PMID:Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum. 1694 Feb 97

Self-associated protein aggregates or cross-linked protein conjugates are, in general, more immunogenic than oligomeric or monomeric forms. In particular, the immunogenicity in mice of a recombinant malaria transmission blocking vaccine candidate, the ookinete specific Plasmodium falciparum 25 kDa protein (Pfs25), was increased more than 1000-fold when evaluated as a chemical cross-linked protein-protein conjugate as compared to a formulated monomer. Whether alternative approaches using protein complexes improve the immunogenicity of other recombinant malaria vaccine candidates is worth assessing. In this work, the immunogenicity of the recombinant 42 kDa processed form of the P. falciparum merozoite surface protein 1 (MSP1(42)) was evaluated as a self-associated, non-covalent aggregate and as a chemical cross-linked protein-protein conjugate to ExoProtein A, which is a recombinant detoxified form of Pseudomonas aeruginosa exotoxin A. MSP1(42) conjugates were prepared and characterized biochemically and biophysically to determine their molar mass in solution and stoichiometry, when relevant. The immunogenicity of the MSP1(42) self-associated aggregates, cross-linked chemical conjugates and monomers were compared in BALB/c mice after adsorption to aluminum hydroxide adjuvant, and in one instance in association with the TLR9 agonist CPG7909 with an aluminum hydroxide formulation. Antibody titers were assessed by ELISA. Unlike observations made for Pfs25, no significant enhancement in MSP1(42) specific antibody titers was observed for any conjugate as compared to the formulated monomer or dimer, except for the addition of the TLR9 agonist CPG7909. Clearly, enhancing the immunogenicity of a recombinant protein vaccine candidate by the formation of protein complexes must be established on an empirical basis.
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PMID:Immunogenicity of self-associated aggregates and chemically cross-linked conjugates of the 42 kDa Plasmodium falciparum merozoite surface protein-1. 2267 76