Antigenic variation in Plasmodium falciparum : understanding the RIFIN protein family

<p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p><h3>List of scientific papers</h3><p>I. Joannin N, Abhiman S, Sonnhammer EL, Wahlgren M. (2008). "Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family." BMC Genomics 15: 19 <br><a href="https://pubmed.ncbi.nlm.nih.gov/18197962">https://pubmed.ncbi.nlm.nih.gov/18197962</a><br><br></p><p>II. Joannin N*, Kallberg Y*, Wahlgren M, Persson B (2010). "RSpred, a set of hidden Markov models to detect and classify the RIFIN and STEVOR proteins of Plasmodium falciparum" (Submitted)</p><p>III. Joannin N, Enquist K, Wahlgren M, von Heijne G, Nilsson I (2010). "RIFIN topology: a new perspective on Plasmodium falciparum variable surface antigens" (Manuscript)</p><p>IV. Hayes CN, Diez D, Joannin N, Honda W, Kanehisa M, Wahlgren M, Wheelock CE, Goto S. (2008). "varDB: a pathogen-specific sequence database of protein families involved in antigenic variation." Bioinformatics 24: 2564-2565 <br><a href="https://pubmed.ncbi.nlm.nih.gov/18776192">https://pubmed.ncbi.nlm.nih.gov/18776192</a><br><br></p>