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 cloning of TRAP1 and hsp75 by yeast two-hybrid screens. Careful analysis of the human TRAP1 and hsp75 sequences revealed that they are identical, and we have cloned a similar protein from Drosophila. Immunofluorescence data show that human TRAP1 is localized to mitochondria. This mitochondrial localization is supported by the existence of mitochondrial localization sequences in the amino termini of both the human and Drosophila proteins. Due to the striking homology of TRAP1 to hsp90, we tested the ability of TRAP1 to function as an hsp90-like chaperone. TRAP1 did not form stable complexes with the classic hsp90 co-chaperones p23 and Hop (p60). Consistent with these observations, TRAP1 had no effect on the hsp90-dependent reconstitution of hormone binding to the progesterone receptor in vitro, nor could it substitute for hsp90 to promote maturation of the receptor to its hormone-binding state. However, TRAP1 is sufficiently conserved with hsp90 such that it bound ATP, and this binding was sensitive to the hsp90 inhibitor geldanamycin. In addition, TRAP1 exhibited ATPase activity that was inhibited by both geldanamycin and radicicol. Thus, TRAP1 has functions that are distinct from those of hsp90.
Felts
S J
SJ
Department of Biochemistry, Mayo Graduate School, Rochester, Minnesota 55905, USA. felts.sara@mayo.edu
Owen
B A
BA
Nguyen
P
P
Trepel
J
J
Donner
D B
DB
Toft
D O
DO
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins; C092306:TRAP1 protein, human; C581704:Trap1 protein, Drosophila