A CORE ATPASE, HSP70-LIKE STRUCTURE IS CONSERVED IN HUMAN, RAT, AND C-ELEGANS STCH PROTEINS

We have identified the rat and Caenorhabditis elegans homologues of a 'core ATPase'-encoding Hsp70-like gene, designated Stch. We observed t hat the human, rat, and C. elegans Stch genes have conserved a stop co don immediately distal to the sequence encoding the Hsp70 ATPase domai n. This results in the functional equivalent of an N-terminal, proteol ytically cleaved fragment of Hsc70/BiP. Each homologue contains a hydr ophobic signal sequence, demonstrates striking identity within the Hsp 70 ATPase domain, and retains a similar C-terminal sequence (STCH spec ific cluster III) that is unique among Hsp70 proteins and which trunca tes the peptide binding domain. In addition, we have identified an int ernal 35-aa region that is homologous to the minimal sequence of the H ip chaperone co-factor that is required for direct binding to the ATPa se domain of Hsp70. Adjacent to this region, the rat and human STCH pr otein sequences diverge within a short internal 'insertion' sequence t hat interrupts the ATPase subdomain between the phosphate-2 and adenos ine ATP-binding sites. We have also demonstrated that both human and r at Stch are constitutively produced and are induced by the calcium ion ophore A23187, but not by heat shock. The recognition that the truncat ed 'core ATPase' structure of the STCH molecule is conserved in human, rat, and C. elegans tissues suggests an important role for this uniqu e member of the membrane-bound Hsp70 family. (C) 1997 Elsevier Science B.V.