A module of the DnaJ heat shock proteins found in malaria parasites.

Abstract

The DnaJ heat shock protein of Escherichia coil plays an essential role in the chaperone function of the hsp70-1ike DnaK protein[ DnaJ stimulates the ATPase activity of DnaK 2 and also directly interacts with specific substrates of the DnaK chaperone machinery ~'3. Several proteins of Saccharomyces cerevisiae possess extensive sequence homologies to DnaJ 4-7 and a human homologue has also been identified s. Sequence alignments suggest four areas of homologyS'6: a low homology region generally found at the carboxy-terminal end, a glycine-rich region, a domain containing four CXXCXGXG motifs and a more highly conserved region often found near the amino terminus. The yeast protein Sec63 contains only the region of highest homology and this is located away from the amino terminus, between two of its three putative membrane-spanning segments 4 (Fig. la). Thus, the DnaJ family shows typical features of mosaic proteins 9 which contain different building units (modules) with separate functions. A database search with sequence consensus patterns m of the most conserved (amino-terminal) domain of DnaJ revealed a surprising similarity to the ring-infected erythrocyte surface antigen (RESA) n of the malaria parasite Plasmodium falciparum. The sequence identity to DnaJ is as high as 39% over a length of 70 residues (Fig. lb), only slightly below that of Sec63 (42%), higher than that of the human DnaJ-like protein (37%), and clearly above the threshold for structural homology of globular proteins m. RESA contains two glutamate- rich regions, one next to the homologous segment and the other one at the carb~xyl terminus (Fig. la). An equivalent acidic region is also found in Sec63 (Fig. la) confirming the modular architecture of both proteins. RESA is an important non-polymorphic malaria antigen m that has been shown to confer some degree of protective immunity on monkeys