HSP90 Alpha Human

Heat Shock Protein-90 Alpha (Hsp90α) is a molecular chaperone that plays a crucial role in maintaining cellular homeostasis. It is one of the most abundant proteins in unstressed cells, constituting 1-2% of the total cellular protein under normal conditions . The “90” in Hsp90 refers to its molecular weight of approximately 90 kilodaltons (kDa) .

Hsp90 was first identified as a stress-responsive protein, induced by heat shock or other stress conditions that cause protein denaturation . It is now known that Hsp90 also has essential functions in unstressed cells, including protein folding, stabilization, and degradation . Hsp90α, specifically, is encoded by the HSP90AA1 gene and is inducible under stress conditions .

There are two main isoforms of Hsp90 in the cytosol of mammalian cells: Hsp90α and Hsp90β. These isoforms share over 85% amino acid sequence identity . Hsp90α is stress-inducible, while Hsp90β is constitutively expressed . The structure of Hsp90 consists of three main domains: the N-terminal domain, the middle domain, and the C-terminal domain . These domains are involved in ATP binding, protein binding, and the chaperone cycle .

Hsp90 functions as a molecular chaperone by recognizing and binding to newly synthesized and partially folded polypeptides, preventing their incorrect folding and aggregation . It is also involved in the trafficking of proteins through the plasma membrane, DNA replication, signal transduction, and the stabilization and activation of a wide range of client proteins . These client proteins play essential roles in cell signaling and adaptive responses to stress .

Hsp90α has been implicated in various diseases, including cancer. It stabilizes several proteins required for tumor growth, making it a target for anti-cancer drugs . Hsp90 inhibitors are being investigated for their potential to disrupt the function of Hsp90 and inhibit tumor growth .

Recombinant Hsp90α is produced using genetic engineering techniques, often expressed in baculovirus systems . This allows for the production of large quantities of Hsp90α for research and therapeutic purposes. Recombinant Hsp90α retains the functional properties of the native protein, making it a valuable tool for studying the molecular mechanisms of Hsp90 and developing potential therapeutic interventions .