Biology:Reticulocyte binding protein homologs
| Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5), coiled-coil domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Rf5 | ||||||||
| Pfam | PF18515 | ||||||||
| InterPro | IPR041668 | ||||||||
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Reticulocyte binding protein homologs (RHs) are a superfamily of proteins found in Plasmodium responsible for cell invasion. Together with the family of erythrocyte binding-like proteins (EBLs) they make up the two families of invasion proteins universal to Plasmodium.[1] The two families function cooperatively.[2]
This family is named after the reticulocyte binding proteins in P. vivax, a parasite that only infects reticulocytes (immature red blood cells) expressing the Duffy antigen. Homologs have since been identified in P. yoelii and P. reichenowi.[1]
A P. falciparum protein complex called PfRH5-PfCyRPA-PfRipr (RCR) is known to bind basigin via the tip of RH5.[3] The trimeric complex forms an elongated structure with RH5 and Ripr on distal ends and CyRPA in the middle.[4] The RCR complex has been identified as a promising malaria vaccine target with each individual component capable of inducing strain transcending immunity in in vitro assays of parasite growth.[5] Of the entire family of RHs, only RH5 appears to be essential for invasion and functions downstream of the other RHs during invasion.[6]
PfRH4 is known to bind complement receptor 1.[7]
RHs do not express any significant sequence feature for specific domains, except for a set of transmembrane helices at the C-terminal. From experimentation on partial proteins, RHs are known to contain enterocyte-binding and nucleotide-sensing domains (EBD and NBD) that may partially overlap. The structure of the EBD has been experimentally observed in 2011 by small angle X-ray scattering.[8] A much better crystal structure for an N-terminal receptor-binding domain (presumably the same as EBD) was published in 2014.[3]
References
- ↑ 1.0 1.1 "Invasion of host cells by malaria parasites: a tale of two protein families". Molecular Microbiology 65 (2): 231–49. July 2007. doi:10.1111/j.1365-2958.2007.05791.x. PMID 17630968.
- ↑ "Reticulocyte and erythrocyte binding-like proteins function cooperatively in invasion of human erythrocytes by malaria parasites". Infection and Immunity 79 (3): 1107–17. March 2011. doi:10.1128/IAI.01021-10. PMID 21149582.
- ↑ 3.0 3.1 "Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies". Nature 515 (7527): 427–30. November 2014. doi:10.1038/nature13715. PMID 25132548. Bibcode: 2014Natur.515..427W.
- ↑ "Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex". Nature 565 (7737): 118–121. January 2019. doi:10.1038/s41586-018-0779-6. PMID 30542156.
- ↑ "The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target". Trends in Parasitology 36 (6): 545–559. June 2020. doi:10.1016/j.pt.2020.04.003. PMID 32359873.
- ↑ "The Molecular Basis of Erythrocyte Invasion by Malaria Parasites". Cell Host & Microbe 22 (2): 232–245. August 2017. doi:10.1016/j.chom.2017.07.003. PMID 28799908.
- ↑ "Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand". Proceedings of the National Academy of Sciences of the United States of America 107 (40): 17327–32. October 2010. doi:10.1073/pnas.1008151107. PMID 20855594. Bibcode: 2010PNAS..10717327T.
- ↑ "Structural characterization of the erythrocyte binding domain of the reticulocyte binding protein homologue family of Plasmodium yoelii". Infection and Immunity 79 (7): 2880–8. July 2011. doi:10.1128/IAI.01326-10. PMID 21482683.
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