LÄHDE: Joannin, Nicolas. Antigenic variation in Plasmodium falciparum : understanding the RIFIN protein family. 2010 Sth.
ISBN: 978-91-7457-075-05
Suomennosta (Abstract)
- RIFIN proteins are variable surface antigens, which have a central role in the survival and virulence of the malaria parasite Plasmodium falciparum.
- Antigenic variation is a mean for these parasites to avoid clearance by the host’s immune system.
- However, this is often a secondary function to the main role of these proteins.
- In the case of RIFIN, P. falciparum’s largest multicopy protein family, the main functions remain unknown.
- In order to elucidate a protein’s function, it is crucial to understand its basic properties, including the structure of the protein family, their localization and the protein’s topology.
- Through different methods, we have strived to simplify the RIFIN protein family into manageable entities.
- We have started with a simple classification of RIFIN proteins into meaningful sub-groups.
- We have predicted that these sub-groups are functionally distinct, although they probably share a related function.
- We then designed RSPred, an automatic method, based on hidden Markov models and a sorting program, to detect and classify RIFIN and STEVOR sequences according to their sub-group.
- Finally, using an in vitro method to determine protein topology, we have analyzed both A-RIFIN and B-RIFIN proteins for their number of transmembrane segments and their topologies.
- We show that both protein groups have a signal sequence targeting them to lipid bilayers and only one transmembrane domain.
- They both share a common topology where the bulk of the protein is exposed to the extracellular environment.
- With the current knowledge of RIFIN protein localizations, as well as the loss of expression of A-RIFIN but not B-RIFIN proteins in a splenectomized patient, it seems increasingly clear that B-RIFIN proteins are good targets for future studies, to decipher the functions of these variable proteins.
Figure 1: Red blood cell infected with Plasmodiumfalciparum.
Antigens expressed at the surface of the blood cell are shown (bottom), as well as the end of chromosome 3 (top), where Bowman et al.1 have identified the genes that encode these proteins. The antigens are highly variable, particularly those encoded by members of the var and rif gene families (PfEMP1 and rifin, respectively). There are roughly 50 var genes, although only one is expressed at a time11,12. By contrast, several of the 200 or so rif gene products may be present on the surface of the same red blood cell. The clag gene family is smaller, and it is not yet clear whether the proteins encoded by these genes are expressed at the surface of the red blood cell7. However, parasites that lack the clag gene on chromosome 9 adhere poorly to host cells10. (Yellow boxes depict genes encoding proteins of unknown function.)
High resolution image and legend (30K)
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