sequence conservation in plasmodium falciparum α-helical coiled coil domains proposed for vaccine development序列保护在恶性疟原虫α-helical卷曲螺旋领域提出了疫苗的发展.pdfVIP

Sequence Conservation in Plasmodium falciparum a- Helical Coiled Coil Domains Proposed for Vaccine Development 1 2 3 1 Caroline Kulangara , Andrey V. Kajava , Giampietro Corradin , Ingrid Felger * 1 Swiss Tropical Institute, Basel, Switzerland, 2 Centre de Recherches de Biochimie Macromoleculaire, FRE-2593 CNRS, Montpellier, France, 3 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland Abstract Background: The availability of the P. falciparum genome has led to novel ways to identify potential vaccine candidates. A new approach for antigen discovery based on the bioinformatic selection of heptad repeat motifs corresponding to a- helical coiled coil structures yielded promising results. To elucidate the question about the relationship between the coiled coil motifs and their sequence conservation, we have assessed the extent of polymorphism in putative a-helical coiled coil domains in culture strains, in natural populations and in the single nucleotide polymorphism data available at PlasmoDB. Methodology/Principal Findings: 14 a-helical coiled coil domains were selected based on preclinical experimental evaluation. They were tested by PCR amplification and sequencing of different P. falciparum culture strains and field isolates. We found that only 3 out of 14 a-helical coiled coils showed point mutations and/or length polymorphisms. Based on promising immunological results 5 of these peptides were selected for further analysis. Direct sequencing of field samples from Papua New Guinea and Tanzania showed that 3 out of these 5 peptides were completely conserved. An in silico analysis of polymorphism was performed for all 166 putative a-helical coiled coi