The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo.
The majority of mouse HSP90 exists as alpha-alpha and beta-beta homodimers. Truncation of the 15-kDa carboxy-terminal region of mouse HSP90 by digestion with the Ca(2+)-dependent protease m-calpain caused dissociation of the dimer. When expressed in a reticulocyte lysate, the full-length human HSP90 alpha formed a dimeric form. A plasmid harboring human HSP90 alpha cDNA was constructed so that the carboxy-terminal 49 amino acid residues were removed when translated in vitro. This carboxy-terminally truncated human HSP90 alpha was found to exist as a monomer. In contrast, loss of the 118 amino acid residues from the amino terminus of human HSP90 alpha did not affect its in vitro dimerization. Introduction of an expression plasmid harboring the full-length human HSP90 alpha complements the lethality caused by the double mutations of two HSP90-related genes, hsp82 and hsc82, in a haploid strain of Saccharomyces cerevisiae. The carboxy-terminally truncated human HSP90 alpha neither formed dimers in yeast cells nor rescued the lethal double mutant.
Minami
Y
Y
Department of Cell Biology, Tokyo Metropolitan Institute of Medical Science, Japan.
Kimura
Y
Y
Kawasaki
H
H
Suzuki
K
K
Yahara
I
I
D000595:Amino Acid Sequence; D000818:Animals; D002154:Calpain / Q000302:isolation & purification / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007940:Leukemia L5178 / Q000378:metabolism; D046911:Macromolecular Substances; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D010446:Peptide Fragments / Q000737:chemistry; D014176:Protein Biosynthesis; D011817:Rabbits; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D010446:Peptide Fragments; D002154:Calpain