The PlasmoDB IDs and chromosome locations are shown for each one of the genes. Comparison of the gene structure with their corresponding cDNAs indicates that pfsr12 and pfsr25 genes contain introns, whereas pfsr1 and pfsr10 do not. This was confirmed for pfsr10, pfsr12 and pfsr25 by sequencing the products amplified by RT-PCR with primers matching to the 59 and 39- ends of the predicted ORFs. We were, however, not able to amplify the pfsr1 full-length ORF from cDNA samples. The different P. falciparum serpentine receptor-like predicted Gefitinib proteins vary in their sizes: the largest translated ORF belongs to PfSR1 and the shortest belongs to PfSR25. It is known that different topology prediction programs vary in their performances. We decided to compare the membrane topology predictions for the four different proteins using four additional programs. As shown in Table 1, the great majority of the programs predict seven TMs for all of the proteins, indicating that our initial predictions were correct. We also used the SignalP algorithm to scan the putative receptors for the presence of signal peptides and their cleavage sites. Potential signal peptides were identified for PfSRs10, 12 and 25. Although no signal peptides were predicted by SignalP for PfSR1, other four transmembrane prediction programs pointed to the presence of an N-terminal signal peptide as shown in Table 1. Vertebrate PfSRs are divided into three main families based on sequence similarity: family A, family B and family C. Usually the TM topology pattern is conserved among PfSRs that have the same function or that belong to the same family. Bioinformatic predictions of membrane topologies of the four PfSRs are presented in Figure 2. All proteins have the characteristic seven transmembrane helices connected through loops. The N-terminal regions are located extracellularly and the C-terminal tail is extended into the U0126 cytoplasmic side of the membrane. The lengths of the N-terminal domains are variable in the different receptors. PfSR1 possesses a very large extracellular N-terminal domain, like members of family C, which includes the glutamate metabotropic and GABA receptors. PfSR10 also has a large N-terminal domain ; similar sizes were described for hormone receptors such as the follicle stimulating hormone receptor and the luteinizing hormone receptor, which belong to family A. The other PfSRs have shorter N-terminal domains, the shortest being the one from PfSR25. Several family A members, like odorant, adenosine and adrenalin receptors, also have small N-terminal domains. The loops connecting the TMs are not very variable among the different PfSRs, except for the first intracellular loop in PfSR25, which is longer than the others.