The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties

The hsp90 family of molecular chaperones was expanded recently due to the c loning of TRAP1 and hsp75 by yeast two-hybrid screens. Careful analysis of the human TRAP1 and hsp75 sequences revealed that they are identical, and w e have cloned a similar protein from Drosophila, Immunofluorescence data sh ow that human TRAP1 is localized to mitochondria. This mitochondrial locali zation is supported by the existence of mitochondrial localization sequence s in the amino termini of both the human and Drosophila proteins. Due to th e striking homology of TRAP1 to hsp90, we tested the ability of TRAP1 to fu nction as an hsp90-like chaperone. TRAP1 did not form stable complexes with the classic hsp90 co-chaperones p23 and Hop (p60), Consistent with these o bservations, TRAP1 had no effect on the hsp90-dependent reconstitution of h ormone binding to the progesterone receptor in vitro, nor could it substitu te for hsp90 to promote maturation of the receptor to its hormone-binding s tate. However, TRAP1 is sufficiently conserved with hsp90 such that it boun d ATP, and this binding was sensitive to the hsp90 inhibitor geldanamycin, In addition, TRAP1 exhibited ATPase activity that was inhibited by both gel danamycin and radicicol, Thus, TRAP1 has functions that are distinct from t hose of hsp90.