Antigenic variation in Plasmodium falciparum : understanding the RIFIN protein family
Year: 2010
Type: dissertation
Abstract: RIFIN proteins are variable surface antigens, which have a central role\nin the survival and virulence of the malaria parasite Plasmodium\nfalciparum. Antigenic variation is a mean for these parasites to avoid\nclearance by the host s immune system. However, this is often a secondary\nfunction to the main role of these proteins. In the case of RIFIN, P.\nfalciparum s largest multicopy protein family, the main functions remain\nunknown. In order to elucidate a protein s function, it is crucial to\nunderstand its basic properties, including the structure of the protein\nfamily, their localization and the protein s topology.\n\nThrough different methods, we have strived to simplify the RIFIN protein\nfamily into manageable entities. We have started with a simple\nclassification of RIFIN proteins into meaningful sub-groups. We have\npredicted that these sub-groups are functionally distinct, although they\nprobably share a related function.\n\nWe then designed RSPred, an automatic method, based on hidden Markov\nmodels and a sorting program, to detect and classify RIFIN and STEVOR\nsequences according to their sub-group.\n\nFinally, using an in vitro method to determine protein topology, we have\nanalyzed both A-RIFIN and B-RIFIN proteins for their number of\ntransmembrane segments and their topologies. We show that both protein\ngroups have a signal sequence targeting them to lipid bilayers and only\none transmembrane domain. They both share a common topology where the\nbulk of the protein is exposed to the extracellular environment.\n\nWith the current knowledge of RIFIN protein localizations, as well as the\nloss of expression of A-RIFIN but not B-RIFIN proteins in a\nsplenectomized patient, it seems increasingly clear that B-RIFIN proteins\nare good targets for future studies, to decipher the functions of these\nvariable proteins.
Source: Figshare
Author: Nicolas Joannin
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1864513741