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{{Short description|An overview of the Hsp90 protein family and its biological significance}} | |||
Hsp90, or Heat Shock Protein 90, is a highly conserved molecular chaperone that plays a critical role in the folding, stability, and function of many proteins, particularly those involved in signal transduction, cell cycle control, and protein degradation. It is a member of the heat shock protein family, which is upregulated in response to stress conditions such as elevated temperatures, oxidative stress, and exposure to toxins. | |||
== Structure == | ==Structure and Function== | ||
Hsp90 is a | Hsp90 is a dimeric protein, meaning it consists of two identical subunits. Each subunit is composed of three domains: the N-terminal domain, which binds ATP; the middle domain, which is involved in client protein binding; and the C-terminal domain, which is responsible for dimerization and also contains a second ATP-binding site. | ||
The ATPase activity of Hsp90 is crucial for its function. The binding and hydrolysis of ATP induce conformational changes that are essential for the chaperone cycle, allowing Hsp90 to interact with a wide range of client proteins. These client proteins include kinases, transcription factors, and other signaling molecules, many of which are involved in cancer progression, making Hsp90 a target for cancer therapeutics. | |||
Hsp90 is | |||
== | ==Biological Significance== | ||
Hsp90 is | Hsp90 is involved in the maturation and stabilization of a variety of "client" proteins, many of which are key regulators of cellular homeostasis. It is particularly important in the context of cancer, as many oncogenic proteins are dependent on Hsp90 for their stability and function. Inhibition of Hsp90 can lead to the degradation of these client proteins, thereby suppressing tumor growth. | ||
== | In addition to its role in cancer, Hsp90 is also implicated in neurodegenerative diseases, where it helps in the refolding of misfolded proteins and prevents the aggregation of proteins such as tau and alpha-synuclein. | ||
==Hsp90 Inhibitors== | |||
Given its role in stabilizing oncogenic proteins, Hsp90 has become a target for cancer drug development. Several Hsp90 inhibitors, such as geldanamycin and its derivatives, have been developed and are currently being tested in clinical trials. These inhibitors bind to the ATP-binding site of Hsp90, preventing its chaperone activity and leading to the degradation of client proteins. | |||
==Related Proteins== | |||
Hsp90 is part of a larger family of heat shock proteins, which includes Hsp70, Hsp60, and small heat shock proteins. Each of these proteins has distinct functions but often work together to maintain protein homeostasis within the cell. | |||
==Related pages== | |||
* [[Heat shock protein]] | * [[Heat shock protein]] | ||
* [[ | * [[Molecular chaperone]] | ||
* [[ | * [[Protein folding]] | ||
* [[Cancer]] | * [[Cancer therapy]] | ||
[[Category:Molecular biology]] | |||
[[Category:Proteins]] | [[Category:Proteins]] | ||
[[Category:Chaperone proteins]] | [[Category:Chaperone proteins]] | ||
<gallery> | |||
File:hsp90.jpg|Hsp90 | |||
File:PDB 1ah6 EBI.jpg|Hsp90 | |||
</gallery> | |||
Latest revision as of 22:43, 21 February 2025
An overview of the Hsp90 protein family and its biological significance
Hsp90, or Heat Shock Protein 90, is a highly conserved molecular chaperone that plays a critical role in the folding, stability, and function of many proteins, particularly those involved in signal transduction, cell cycle control, and protein degradation. It is a member of the heat shock protein family, which is upregulated in response to stress conditions such as elevated temperatures, oxidative stress, and exposure to toxins.
Structure and Function[edit]
Hsp90 is a dimeric protein, meaning it consists of two identical subunits. Each subunit is composed of three domains: the N-terminal domain, which binds ATP; the middle domain, which is involved in client protein binding; and the C-terminal domain, which is responsible for dimerization and also contains a second ATP-binding site.
The ATPase activity of Hsp90 is crucial for its function. The binding and hydrolysis of ATP induce conformational changes that are essential for the chaperone cycle, allowing Hsp90 to interact with a wide range of client proteins. These client proteins include kinases, transcription factors, and other signaling molecules, many of which are involved in cancer progression, making Hsp90 a target for cancer therapeutics.
Biological Significance[edit]
Hsp90 is involved in the maturation and stabilization of a variety of "client" proteins, many of which are key regulators of cellular homeostasis. It is particularly important in the context of cancer, as many oncogenic proteins are dependent on Hsp90 for their stability and function. Inhibition of Hsp90 can lead to the degradation of these client proteins, thereby suppressing tumor growth.
In addition to its role in cancer, Hsp90 is also implicated in neurodegenerative diseases, where it helps in the refolding of misfolded proteins and prevents the aggregation of proteins such as tau and alpha-synuclein.
Hsp90 Inhibitors[edit]
Given its role in stabilizing oncogenic proteins, Hsp90 has become a target for cancer drug development. Several Hsp90 inhibitors, such as geldanamycin and its derivatives, have been developed and are currently being tested in clinical trials. These inhibitors bind to the ATP-binding site of Hsp90, preventing its chaperone activity and leading to the degradation of client proteins.
Related Proteins[edit]
Hsp90 is part of a larger family of heat shock proteins, which includes Hsp70, Hsp60, and small heat shock proteins. Each of these proteins has distinct functions but often work together to maintain protein homeostasis within the cell.
Related pages[edit]
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Hsp90 -
Hsp90
