Merozoite surface proteins are both integral and peripheral membrane

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s found on the surface of a

merozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...

, an early life cycle stage of a

protozoan Protozoa (: protozoan or protozoon; alternative plural: protozoans) are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically ...

. Merozoite surface proteins, or MSPs, are important in understanding

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

, a disease caused by protozoans of the genus ''

Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a Hematophagy, blood-feeding insect host (biology), host which then inj ...

''. During the asexual blood stage of its life cycle, the malaria parasite enters

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

s to replicate itself, causing the classic symptoms of malaria. These surface protein complexes are involved in many interactions of the parasite with red blood cells and are therefore an important topic of study for scientists aiming to combat malaria.

Forms

The most common form of MSPs are anchored to the merozoite surface with

glycophosphatidylinositol Glycosylphosphatidylinositol () or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide vari ...

, a short

glycolipid Glycolipids () are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the c ...

often used for protein anchoring. Additional forms include integral membrane proteins and peripherally associated proteins, which are found to a lesser extent than glycophosphatidylinositol anchored proteins, or (GPI)-anchored proteins, on the merozoite surface. Merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) are the most abundant (GPI)-anchored proteins on the surface of Plasmodium merozoites.

Function

MSP-1 is synthesized at the very beginning of

schizogony Fission, in biology, is the division of a single entity into two or more parts and the regeneration of those parts to separate entities resembling the original. The object experiencing fission is usually a cell, but the term may also refer to ho ...

, or asexual merozoite reproduction. The merozoite first attaches to a red blood cell using its MSP-1 complex. The MSP-1 complex targets

spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma mem ...

, a complex on the internal surface of the cell membrane of a red blood cell. The majority of the MSP-1 complex is shed upon entry into the red blood cell, but a small portion of the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

, called MSP-1₁₉, is conserved. The exact role of MSP-1₁₉ remains unknown, but it currently serves as a marker for the formation of the

food vacuole The food vacuole, or digestive vacuole, is an organelle found in simple eukaryotes such as protists. This organelle is essentially a lysosome. During the stage of the symbiont parasites' lifecycle where it resides within a human (or other mammalia ...

. The function of the MSP-2 complex is not concrete, but current research suggests it has a role in red blood cell invasion due to its degradation shortly after invasion. MSP- 3, 6, 7 and 9 are peripheral membrane proteins that have been shown to form a complex with MSP-1, but the functions of these proteins are largely unknown.

Clinical significance

Due to their prevalence on the Plasmodium surface, MSPs have been a key target for

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

development. Anti-malarial vaccines have been developed to target the merozoite at different stages in its life cycle. Vaccines that target the merozoite in its asexual erythrocytic stage utilize merozoite surface proteins, particularly MSP-1. In addition to vaccines, researchers are developing drugs that bind to MSPs in order to disrupt merozoite replication.

Suramin Suramin is a medication used to treat African sleeping sickness and river blindness. It is the treatment of choice for sleeping sickness without central nervous system involvement. It is given by injection into a vein. Suramin causes a fai ...

, a drug used to treat African sleeping sickness, has shown moderate success with binding to MSP-1 and its derivatives such as MSP-1₁₉ to inhibit red blood cell invasion.

Challenges

The challenge faced when developing vaccines is the complexity and variation of these proteins. In merozoites of the same genus and species, the sequences encoding proteins such as MSP-1 vary depending on the region they are found. For example, the Combination B vaccine utilizes

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s of MSP-1 and MSP-2 but has limited efficacy based primarily on the MSP-2

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

s used. In an attempt to increase the efficiency of vaccines produced, constant regions such as MSP-1₁₉ which remain on the surface of the Plasmodium after the merozoite stage are becoming a key focus for vaccine studies. Additionally, synthetic

(GPI) molecules are candidates since they elicit a strong immune response while simultaneously remaining relatively consistent in structure over various malarial strains. Also MSP3 is being studied as a vaccine antigen.

References

{{DEFAULTSORT:Merozoite Surface Protein Parasitology Apicomplexan proteins Malaria