Hsp90α (human recombinant)

Heat shock protein 90 α (Hsp90α) is the inducible cytosolic isoform of Hsp90 that is encoded by HSP90AA in humans.¹ Hsp90 is a multidomain protein that functions as a molecular chaperone to assist in folding and activation of nascent peptides, refolding unfolded or misfolded proteins, and preventing protein aggregation.² C-terminal dimerization of Hsp90, coupled with ATPase molecular clamp activity induces a conformational change in the N-terminal nucleotide binding domain that facilitates substrate binding and initiates the chaperone cycle.³ Hsp90 interacts with many co-chaperones during its chaperone cycle including p23 and Sba1, which help recruit substrates to the Hsp90 complex, Hsp70 (Item Nos. 22739 | 23002), which loads nascent polypeptides onto the Hsp90 dimer, and the ATPase activator Aha1 that promotes ATP hydrolysis and substrate release.^4,5 Hsp90 is overexpressed in cancer cells and stabilizes client proteins that promote oncogenesis, including transcription factors, signaling proteins, and kinases.^1,5 Hsp90 also decreases α-synuclein fibril formation and toxicity as well as Q35 aggregation in in vitro models of Parkinson's and Huntington's disease, respectively, implying a role in neurodegenerative disease.⁶

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1. Chen, B., Piel, W.H., Gui, L., et al. The HSP90 family of genes in the human genome: Insights into their divergence and evolution. Genomics 86(6), 627-637 (2005).

2. Fink, A.L. Chaperone-mediated protein folding. Physiol. Rev. 79(2), 425-449 (1999).

3. Prodromou, C., Panaretou, B., Chohan, S., et al. The ATPase cycle of Hsp90 drives a molecular “clamp” via transient dimerization of the N-terminal domains. EMBO J. 19(16), 4383-4392 (2000).

4. Ali, M.M.U., Roe, S.M., Vaughan, C.K., et al. Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440(7087), 1013-1017 (2006).

5. Li, J., and Buchner, J. Structure, function and regulation of the hsp90 machinery. Biomed. J. 36(3), 106-117 (2013).

6. Lackie, R.E., Maciejewski, A., Ostapchenko, V.G., et al. The Hsp70/Hsp90 chaperone machinery in neurodegenerative diseases. Front. Neurosci. 11:254, (2017).