THE MITOCHONDRIAL HSP70 CHAPERONE SYSTEM - EFFECT OF ADENINE-NUCLEOTIDES, PEPTIDE SUBSTRATE, AND MGRPE ON THE OLIGOMERIC STATE OF MHSP70

Mitochondrial hsp70 (mhsp78) is a key component in the import and fold ing of mitochondrial proteins. In both processes, mhsp70 cooperates wi th the mitochondrial nucleotide exchange factor mGrpE (also termed Mge 1p). In this work we have characterized the self-association of purifi ed mhsp70, the interaction of mhsp70 with isolated mGrpE and protein s ubstrate, and the effect of nucleotides on these interactions, mhsp70 can form oligomers that are dissociated by ATP or by a nonhydrolyzable ATP analog, A substrate peptide binds to mhsp70 in the absence of add ed nucleotides and is released by ATP but not by ADP. Binding of the p eptide causes nucleotide-independent dissociation of the mhsp70 oligom ers and enhances the mhsp70 ATPase. Purified mGrpE forms a homodimer, In the absence of added nucleotides, one mGrpE dimer binds to one mole cule of mhsp70, forming a stable 122 kDa hetero-oligomer, This complex is weakened by ADP and completely dissociated by ATP.