ANALYSIS OF A CATION-TRANSPORTING ATPASE OF PLASMODIUM-FALCIPARUM

We have cloned and characterised one gene, PfATPase4 which encodes a P -type ATPase containing all the primary sequence motifs characteristic of this class of transmembrane ion transporters, and also a fragment of a second P. falciparum P-type ATPase pseudogene (PfATPase5). Analys is of conserved domains and motifs of specific ATPases reveals that Pf ATPase4 is most analogous to Ca2+ ATPases of the endoplasmic reticulum . The PfATPase4 gene gives rise to a transcript of 8 kb shortly after erythrocyte invasion. Although this mRNA is not detected in later stag es, the protein detected immunologically at 190 kDa persists throughou t and is detected in free merozoites. Immunofluorescence microscopy re veals that the PfATPase4 protein is concentrated in discrete compartme nts at the periphery of the parasite. Detailed sequence and structural analyses of these and the other P-type ATPases of P. falciparum descr ibed previously, reveals that they comprise an unusual family in sever al respects. Firstly, the large number of non-homologous genes so far characterised reflects the complexities of ionic regulation in the div erse environments encountered by the parasite. Secondly, the plasmodia l P-type ATPase family may be classified both at primary sequence and structural levels into two distinct groups - those typical of P-type A TPases (including PfATPase4) and those which are much more divergent. A third complexity is illustrated by the fact that one of the other me mbers [1] here termed PfATPase6, has an even greater similarity to the sarcoplasmic reticulum Ca2+ ATPases than does PfATPase4 which raises questions about the possible functional relationship between these two members.