Biology:Merozoite surface protein
| Merozoite Surface Protein-1 | |||||||
|---|---|---|---|---|---|---|---|
 The MSP-1 complex is attached to the merozoite cell membrane via GPI-anchoring, indicated by the staggered lines penetrating the cell membrane. After red blood cell invasion, the majority of the MSP-1 complex is shed, leaving MSP-119 behind.[1] | |||||||
| Identifiers | |||||||
| Organism | |||||||
| Symbol | MSP1 | ||||||
| Alt. symbols | PKH_072850 [2] | ||||||
| Entrez | 7320035 | ||||||
| PDB | 1N1I (ECOD) | ||||||
| RefSeq (mRNA) | XM_002258546.1 | ||||||
| RefSeq (Prot) | XP_002258582.1 | ||||||
| UniProt | Q9GSQ9 | ||||||
| Other data | |||||||
| Chromosome | 7: 1.26 - 1.27 Mb | ||||||
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Merozoite /ˌmɛrəˈzoʊˌaɪt/ surface proteins are both integral and peripheral membrane proteins found on the surface of a merozoite, an early life cycle stage of a protozoan.[1] Merozoite surface proteins, or MSPs, are important in understanding malaria, a disease caused by protozoans of the genus Plasmodium. During the asexual blood stage of its life cycle, the malaria parasite enters red blood cells to replicate itself, causing the classic symptoms of malaria.[3] 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.[4]
Forms
The most common form of MSPs are anchored to the merozoite surface with glycophosphatidylinositol, a short glycolipid 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.[4] Merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) are the most abundant (GPI)-anchored proteins on the surface of Plasmodium merozoites.[4]
Function
MSP-1 is synthesized at the very beginning of schizogony, or asexual merozoite reproduction.[5] The merozoite first attaches to a red blood cell using its MSP-1 complex. The MSP-1 complex targets spectrin, a complex on the internal surface of the cell membrane of a red blood cell.[citation needed] The majority of the MSP-1 complex is shed upon entry into the red blood cell, but a small portion of the C-terminus, called MSP-119, is conserved.[6] The exact role of MSP-119 remains unknown, but it currently serves as a marker for the formation of the food vacuole.[1]
File:Merozoite Surface Protein-1 Segments from Sequence Processing.tif
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.[4] 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.[4]
Clinical significance
Due to their prevalence on the Plasmodium surface, MSPs have been a key target for vaccine 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.[8] In addition to vaccines, researchers are developing drugs that bind to MSPs in order to disrupt merozoite replication.[9] Suramin, 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.[10]
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.[11] For example, the Combination B vaccine utilizes antigens of MSP-1 and MSP-2 but has limited efficacy based primarily on the MSP-2 alleles used.[12] 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.[4] Additionally, synthetic glycophosphatidylinositol (GPI) molecules are candidates since they elicit a strong immune response while simultaneously remaining relatively consistent in structure over various malarial strains.[13] Also MSP3 is being studied as a vaccine antigen.[14]
References
- ↑ 1.0 1.1 1.2 "Merozoite surface proteins of the malaria parasite: the MSP1 complex and the MSP7 family". International Journal for Parasitology 40 (10): 1155–61. August 2010. doi:10.1016/j.ijpara.2010.04.008. PMID 20451527.
- ↑ "PKH_072850 merozoite surface protein 1, MSP-1 [ Plasmodium knowlesi strain H "]. Entrez Gene. National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/gene/7320035.
- ↑ "Molecular Signaling Involved in Entry and Exit of Malaria Parasites from Host Erythrocytes". Cold Spring Harbor Perspectives in Medicine 7 (10): a026815. October 2017. doi:10.1101/cshperspect.a026815. PMID 28507195.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria". FEMS Microbiology Reviews 40 (3): 343–72. May 2016. doi:10.1093/femsre/fuw001. PMID 26833236.
- ↑ "The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria". Parasitology 136 (12): 1445–56. October 2009. doi:10.1017/S0031182009990515. PMID 19627632.
- ↑ "A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies". The Journal of Experimental Medicine 172 (1): 379–82. July 1990. doi:10.1084/jem.172.1.379. PMID 1694225.
- ↑ "Antibodies against multiple merozoite surface antigens of the human malaria parasite Plasmodium falciparum inhibit parasite maturation and red blood cell invasion". Malaria Journal 9 (1): 77. March 2010. doi:10.1186/1475-2875-9-77. PMID 20298576.
- ↑ "N-terminal Plasmodium vivax merozoite surface protein-1, a potential subunit for malaria vivax vaccine". Clinical & Developmental Immunology 2013: 965841. 2013. doi:10.1155/2013/965841. PMID 24187566.
- ↑ "Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum". BMC Biology 13: 52. July 2015. doi:10.1186/s12915-015-0162-0. PMID 26187647.
- ↑ "Suramin and suramin analogues inhibit merozoite surface protein-1 secondary processing and erythrocyte invasion by the malaria parasite Plasmodium falciparum". The Journal of Biological Chemistry 278 (48): 47670–7. November 2003. doi:10.1074/jbc.M306603200. PMID 13679371.
- ↑ "Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1)". Molecular and Biochemical Parasitology 59 (1): 1–14. May 1993. doi:10.1016/0166-6851(93)90002-f. PMID 8515771.
- ↑ "Designing malaria vaccines to circumvent antigen variability". Vaccine 33 (52): 7506–12. December 2015. doi:10.1016/j.vaccine.2015.09.110. PMID 26475447.
- ↑ "Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage". Frontiers in Immunology 8: 349. 2017-03-28. doi:10.3389/fimmu.2017.00349. PMID 28400771.
- ↑ Baumann A, Magris MM, Urbaez ML, Vivas-Martinez S, Durán R, Nieves T, Esen M, Mordmüller BG, Theisen M, Avilan L, Metzger WG. Naturally acquired immune responses to malaria vaccine candidate antigens MSP3 and GLURP in Guahibo and Piaroa indigenous communities of the Venezuelan Amazon. Malar J. 2012 Feb 15;11:46. doi: 10.1186/1475-2875-11-46. PMID: 22335967; PMCID: PMC3296639.
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