Structure, Function and Regulation of the Hsp90 Machinery
Jing Li,Johannes Buchner +1 more
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TLDR
The recent progress made in understanding the Hsp90 machinery is discussed, which influences the conformational cycle, co-chaperone interaction, and inter-domain communications.Abstract:
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations ATP binding triggers directionality in these conformational changes and leads to a more compact state To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation They influence the conformational cycle, co-chaperone interaction, and inter-domain communications In this review, we discuss the recent progress made in understanding the Hsp90 machineryread more
Citations
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The role of small GTPase Rac1 in stress signaling
TL;DR: Rac1 is a major mediator of heat stress signal transduction between plasma membrane and prominent HSP genes tested, in melanoma cells and is involved in stress signaling through the effect of stress on membrane microdomain organization.
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An insight to Heat shock protein 90: A remedy for multiple problems.
TL;DR: In this paper , a compilation of the pharmacological profile of heat shock protein 90 inhibitors, problems associated with them, and suggested remedies for the same is presented, where the role of Hsp90 is not only in cancer but also in other diseases like COVID-19, leishmaniasis, diabetes, flavi virus, systemic sclerosis, grass carp reovirus, psoriasis, malaria, cardiac fibrosis, and alcohol-related liver diseases.
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In Silico Docking Studies of Alkannin and Shikonin with Heat Shock Protein-90 (Hsp90)
TL;DR: Alkannin (3) and shikonin (4) may inhibit cancer progressin by binding to the active site of HSP90 comparable to Hsp90 inhibitor drug, geldanamycin (2).
References
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William B. Pratt,David O. Toft +1 more
TL;DR: This purified system of five purified proteins should facilitate understanding of how eukaryotlc hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
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