A conserved region of the MSP-1 surface protein of Plasmodium falciparum contains a recognition sequence for erythrocyte spectrin.

Herrera, Sócrates; Rudin, W.; Herrera, Mario Alain; Clavijo, Pedro; Mancilla, Lida Inés; Plata, Cecilia de; Matile, Hugues; Certa, Ulrich

doi:10.1002/j.1460-2075.1993.tb05805.x

Cited by 27 publications

(29 citation statements)

References 44 publications

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“…The functional role of these repeats is not clear. It is interesting to note that the binding regions of MESA, RESA and MSP-1 mentioned above are all found in non-repetitive domains (33)(34)(35). Previous work that mapped the spectrin-binding domain of KAHRP to a 271-residue region (27), and this region contained the 5Ј-repeat.…”

Section: Discussionmentioning

confidence: 93%

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Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Pei

Guo

et al. 2005

Journal of Biological Chemistry

100

109

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Plasmodium falciparum dramatically modifies the structure and function of the membrane of the parasitized host erythrocyte. Altered membrane properties are the consequence of the interaction of a group of exported malaria proteins with host cell membrane proteins. KAHRP (the knob-associated histidine-rich protein), a member of this group, has been shown to interact with erythrocyte membrane skeletal protein spectrin. However, the molecular basis for this interaction has yet to be defined. In the present study, we defined the binding motifs in both KAHRP and spectrin and identified a functional role for this interaction. We showed that spectrin bound to a 72-amino-acid KAHRP fragment (residues 370 -441). Among nine-spectrin fragments, which encompass the entire ␣ and ␤ spectrin molecules (four ␣ spectrin and five ␤ spectrin fragments), KAHRP bound only to one, the ␣ N-5 fragment. The KAHRP-binding site within the ␣ N-5 fragment was localized uniquely to repeat 4. The interaction of fulllength spectrin dimer to KAHRP was inhibited by repeat 4 of ␣ spectrin. Importantly, resealing of this repeat peptide into erythrocytes mislocalized KAHRP in the parasitized cells. We concluded that the interaction of KAHRP with spectrin is critical for appropriate membrane localization of KAHRP in parasitized erythrocytes. As the presence of KAHRP at the erythrocyte membrane is necessary for cytoadherence in vivo, our findings have implications for the development of new therapies for mitigating the severity of malaria infection.Malaria caused by Plasmodium falciparum is the most serious parasitic disease of humans. Clinical symptoms occur during the asexual stage of the life cycle of the parasites, at which time it multiplies within the human erythrocyte. During intraerythrocytic growth, the parasite extensively modifies the host erythrocyte resulting in alterations of morphology, mechanical properties, and adhesive properties. It is generally believed that almost all the altered properties of parasitized erythrocytes are because of the action of a group of parasite proteins that become associated with erythrocyte membrane proteins (see Refs. 1-3 for recent reviews). Well studied members of this group include the knob-associated histidine-rich protein (KAHRP), 1 P. falciparum erythrocyte membrane protein 1 (PfEMP1), the ring parasite-infected erythrocyte surface antigen (RESA), and the mature parasite-infected erythrocyte surface antigen (MESA).KAHRP, an 85-105-kDa protein that is expressed during the middle and later stages of the asexual cycle (4, 5), has been shown to be critically important for knob formation in infected erythrocytes (6). It interacts with erythrocyte skeletal proteins such as spectrin, actin, and ankyrin (7, 8) and also with erythrocyte membrane-associated parasite protein, PfEMP1 (9). PfEMP1 mediates the adhesion of parasitized erythrocytes to the vascular endothelium (10), a process strongly implicated in the pathology of cerebral malaria (11). The absence of the KAHRP protein at the erythrocyte membrane l...

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Section: Discussionmentioning

confidence: 93%

“…For example, the 4.1R-binding site in MESA has been localized to 19 residues located in the N-terminal region of MESA (35). The spectrin-binding domain in RESA has been mapped to a 48-residue region (33), whereas the spectrin-binding domain in MSP-1 has been localized to a 30-residue region (34).…”

Section: Discussionmentioning

confidence: 99%

Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Pei

Guo

et al. 2005

Journal of Biological Chemistry

100

109

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“…37 The sequence homology found between the Pf190L subunit and Pv200L (> 66% for fragments A and B) and the existence of the HRBI region, which is considered a P. vivax merozoite ligand for reticulocyte binding and invasion, 29 suggest that these are homologous regions with similar functions in both parasites (Figures 1 and 2). In addition to the sequence homology between the two protein fragments, the cross-recognition of the recombinant Pf190L fragment by antibodies to Pv200L elicited in BALB/c mice indicate sharing of B epitopes of the two MSP-1 proteins ( Figure 5).…”

Section: 1617mentioning

confidence: 99%

Antigenicity, Immunogenicity, and Protective Efficacy of Plasmodium Vivax Msp1 Pv200l: A Potential Malaria Vaccine Subunit

Valderrama-Aguirre

Quintero

Gomez

et al. 2005

The American Journal of Tropical Medicine and Hygiene

117

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Abstract. The merozoite surface protein 1 (MSP-1) is expressed in all Plasmodium species and is considered a major malaria vaccine candidate. We found that MSP-1 from Plasmodium vivax (PvMSP-1) contains a region of significant sequence homology with the 190L subunit vaccine derived from the P. falciparum MSP-1. The fragment, termed Pv200L, was expressed as a recombinant protein in Escherichia coli (rPv200L) and used to asses its immunologic relevance as a vaccine target. A cross-sectional, seroepidemiologic study conducted in Buenaventura, Colombia showed that 52.2% (95% confidence interval [CI] ‫ס‬ 39.8-64.3) of individuals previously exposed to P. vivax and 72.8% (95% CI ‫ס‬ 61.8-82.1) of P. vivax-infected patients had IgG antibodies to rPv200L. Immunization of BALB/c mice and Aotus monkeys induced IgG antibodies (titer > 10 6 ) that cross-reacted with P. vivax parasites. Immunized monkeys displayed partial protection against a challenge with P. vivax blood stages. Our results suggest that Pv200L is a new malaria vaccine subunit and deserves further testing.

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“…P. falciparum Knobassociated histidine-rich protein (KAHRP) binds the spectrin 4 repeat specifically before interacting with the erythrocyte skeleton [65]. Finally KAHRP combines with P. falciparum erythrocyte membrane protein 1, which adheres to the parasitized erythrocyte cell on the vascular endothelium [66].…”

Section: The Role Of Spectrin In Diseasementioning

confidence: 99%

Spectrin: Structure, function and disease

Zhang

Zhao

et al. 2013

Sci. China Life Sci.

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Spectrin is a large, cytoskeletal, and heterodimeric protein composed of modular structure of and subunits, it typically contains 106 contiguous amino acid sequence motifs called "spectrin repeats". Spectrin is crucial for maintaining the stability and structure of the cell membrane and the shape of a cell. Moreover, it contributes to diverse cell functions such as cell adhesion, cell spreading, and the cell cycle. Mutations of spectrin lead to various human diseases such as hereditary hemolytic anemia, type 5 spinocerebellar ataxia, cancer, as well as others. This review focuses on recent advances in determining the structure and function of spectrin as well as its role in disease.erythrocyte, spectrin, cell cycle, mass spectrometry, disease Citation:Zhang R, Zhang C Y, Zhao Q, et al. Spectrin: Structure, function and disease.

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A conserved region of the MSP-1 surface protein of Plasmodium falciparum contains a recognition sequence for erythrocyte spectrin.

Cited by 27 publications

References 44 publications

Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Antigenicity, Immunogenicity, and Protective Efficacy of Plasmodium Vivax Msp1 Pv200l: A Potential Malaria Vaccine Subunit

Spectrin: Structure, function and disease

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