A malaria merozoite surface protein (MSP1)-structure, processing and function

Holder, Anthony A.; Blackman, Michael J.; Burghaus, Petra A.; Chappel, Jonathan A.; Ling, Irene T.; McCallum-Deighton, Neil; Shai, Shafrira

doi:10.1590/s0074-02761992000700004

Cited by 175 publications

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“…MSP1 is expressed as a precursor protein of approximately 200 kDa on the surface of developing merozoites [16]. It is proteolytically processed into several fragments at the time of schizont rupture and red cell invasion.…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

Kusi

Remarque

Riasat

et al. 2011

Malar J

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BackgroundIncreasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1) multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo) vaccine candidates formulated as an equimolar mixture (DiCo mix) in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP119 fusion protein formulated in Montanide ISA 51.MethodsVaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains.ResultsThese data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons.ConclusionsThe study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

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Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

Kusi

Remarque

Riasat

et al. 2011

Malar J

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“…MSP-1 is synthesized as a 180 -225-kDa polypeptide capable of binding sialic acid (2,3). As a requirement for merozoite entry into a red cell, MSP-1 undergoes two processing steps, the first at merozoite release from an infected cell and the second during invasion of a red cell (4) (Fig. 1a).…”

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confidence: 99%

“…In the first processing step, the precursor polypeptide is cleaved into four chains (with apparent molecular masses of 83, 30, 38, and 42 kDa) held together by noncovalent contacts (4 -6). In the second processing step, the 42-kDa segment (MSP-1 42 ) is cleaved into two fragments with apparent molecular masses of 33 kDa (MSP-1 33 ) and 19 kDa (MSP-1 19 or MSP-1 inv ) (4). MSP-1 33 sheds from the surface, whereas MSP-1 19 remains anchored to the merozoite membrane by a glycosylphosphatidylinositol tail attached to the C-terminal residue (7)(8)(9)(10).…”

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Structure of the C-terminal Domains of Merozoite Surface Protein-1 from Plasmodium knowlesi Reveals a Novel Histidine Binding Site

Garman¹,

Simcoke²,

Stowers³

et al. 2003

Journal of Biological Chemistry

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The protozoan parasite Plasmodium causes malaria, with hundreds of millions of cases recorded annually. Protection against malaria infection can be conferred by antibodies against merozoite surface protein (MSP)-1, making it an attractive vaccine candidate. Here we present the structure of the C-terminal domains of MSP-1 (known as MSP-1 19 ) from Plasmodium knowlesi. The structure reveals two tightly packed epidermal growth factor-like domains oriented head to tail. In domain 1, the molecule displays a histidine binding site formed primarily by a highly conserved tryptophan. The protein carries a pronounced overall negative charge primarily due to the large number of acidic groups in domain 2. To map protein binding surfaces on MSP-1 19 , we have analyzed the crystal contacts in five different crystal environments, revealing that domain 1 is highly preferred in protein-protein interactions. A comparison of MSP-1 19 structures from P. knowlesi, P. cynomolgi, and P. falciparum shows that, although the overall protein folds are similar, the molecules show significant differences in charge distribution. We propose the histidine binding site in domain 1 as a target for inhibitors of protein binding to MSP-1, which might prevent invasion of the merozoite into red blood cells.

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“…MSP-1 es una glicoproteina que se sintetiza durante los estadios tardíos del desarrollo intraeritrocitario del parásito (después de 36 horas); se encuentra en la membrana plasmática de los estadios maduros y en la superficie de los merozoitos liberados después de la ruptura de la célula infectada. Debido a que MSP-1 es una proteina integral de la membrana plasmática del parásito, expuesta completamente al medio extracelular y anclada a la membrana mediante una molécula de GPI, su extracción requiere el uso de detergentes (2,3).…”

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Producción y caracterización de un anticuerpo monoclonal que reconoce el fragmento 28-30 kDa de la proteína MSP-1 de Plasmodium falciparum

2000

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Los merozoitos del parásito Plasmodium falciparum contienen en su superficie los fragmentos producidos por el primer procesamiento proteolítico de la proteina MSP-1 (rnerozoite surface protein-1). Dichos fragmentos tienen pesos moleculares relativos aproximados de 83, 42. 38 y 28-30 kDa, respectivamente. En este estudio se describe la producción y caracterización de un anticuerpo monoclonal, denominado 8F4, que reconoce la proteina MSP-1 dadas las siguientes características del antigeno: 1) localización subcelular, 2) peso molecular relativo. 3) periodo de expresión durante el ciclo eritrocitico, 4) tipo de asociación con la membrana plasmática del parásito y 5) presencia de epítopes compartidos con MSP-1. Adicionalmente. se estableció que 8F4 reconoce el fragmento de 28-30 kDa, producto del primer procesamiento proteolitico de MSP-1. Los análisis realizados permiten confirmar que MSP-I , ,, , no permanece en la superficie del merozoito desoués de ocurrida la invasión. lo cual suoiere oue hace oarte del comoleio de . . polipéptidos que es liberado por el merozoito previamenie al eiento de ¡a invasibn. 8F4 es el primer anticuerpo monoclonal reportado hasta el momento que reconoce especificamente este fragmento.Palabras clave: malaria, Plasmodium falciparum. MSP-1. anticuerpo monoclonal Production and characterization of a monoclonal antibody that recognizes the fragment of 28-30 kDa of the protein MSP-1 from Plasmodium falciparum Merozoites of the malaria parasite Plasmodium falciparum have on their surface proteolytic processed fragments of MSP-1 (merozoite surface protein-1). These fragments have relative molecularweights of approximately 83. 42, 38, 28-30 kDa, respectively In this study we describe the characterization of a monoclonal antibody. denominated 8F4, that recognizes MSP-1 based upon the following characteristics: 1) subcellular location of the antigen. 2) relative molecular weight, 3) time of expression during the asexual life cycle of the parasite, 4) the association of the protein with the plasma membrane and 5) epitopes shared with MSP-1. In addition, it was found that 8F4 recognizes the 28-30 kDa fragment that arises as a consequence of the first proteolyiic processing of MSP-1. The study confirms that such fragment is excluded from the merozoite surface during invasion, suggesting that it makes part of a complex of polypeptides which is released from the merozoite before the invasion process takes place. This is the first report of a monoclonal antibody which specifically recognizes this polypeptide.Key Words: malaria, Plasmodium falciparurn, MSP-l. monoclonal antibody.Hace siglos, la malaria fue reconocida como una q u e afectan al género humano y pese a la de lasenfermedades parasitarias más importantes introducción de programas de control en muchas partes del mundo durante las décadas pasadas,

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A malaria merozoite surface protein (MSP1)-structure, processing and function

Cited by 175 publications

References 0 publications

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

Structure of the C-terminal Domains of Merozoite Surface Protein-1 from Plasmodium knowlesi Reveals a Novel Histidine Binding Site

Producción y caracterización de un anticuerpo monoclonal que reconoce el fragmento 28-30 kDa de la proteína MSP-1 de Plasmodium falciparum

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