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.
