||November 5, 2007
||Nicolas Joannin, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Sweden
||About RIFINs: from gene family to function, Or the complexity of antigenically variable protein families
|| Some pathogens are capable of persisting within the human host for
long periods of time, causing chronic infections. They survive and
escape immune pressure through extreme polymorphism of the polypeptides
they expose to the host. The Plasmodium falciparum parasite, responsible
for severe disease and mortality in human malaria, is such a pathogen.
The parasite uses strategies for maximizing survival and proliferative
capacity in the blood stage of its life cycle: receptor-mediated binding
of the parasitized red blood cell to human receptors and variation of
antigenic epitopes presented at the surface of the cell.
rif genes are the largest multi-copy gene family of P. falciparum,
with ~150 genes per haploid genome. They are distributed in the
subtelomeric ends of all 14 chromosomes and encode clonally variant
antigens of 30-45 kDa called RIFINs, expressed at the surface of the
parasitized red blood cell (pRBC). We have shown, using bioinformatics
and in vitro tools, that these proteins can be subdivided in two major
groups, which have probably undergone sub-functionalization.
VarDB: why another database? From viruses to parasitic fungi, many
groups around the world work on antigenic variant proteins. However,
they do so independently from one family to another. The varDB project
aims at giving these scientists a platform to exchange knowledge,
resources and ideas about antigenic variation, whichever species or
protein family they work on. Tools specifically developed to analyze
these complex protein families are necessary and will complement its
functionality. VarDB is a needed resource.