Structure, Function and Regulation of the Hsp90 Machinery
Jing Li,Johannes Buchner +1 more
Reads0
Chats0
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
More filters
Journal ArticleDOI
Interaction of E. coli Hsp90 with DnaK Involves the DnaJ Binding Region of DnaK
TL;DR: The results suggest that a specific region in the NBD of DnaK is involved in the interaction with Hsp90Ec, and this interaction is functionally important.
Journal ArticleDOI
The regulation mechanisms of AhR by molecular chaperone complex.
Ikuru Kudo,Miki Hosaka,Asami Haga,Noriko Tsuji,Yuhtaroh Nagata,Hirotaka Okada,Kana Fukuda,Yuka Kakizaki,Tomoya Okamoto,Ewa Grave,Hideaki Itoh +10 more
TL;DR: This study analyzed the direct interaction of bHLH with HSP90, p23 and XAP2 using purified proteins and found that not only the PAS domain but also the b HLH domain bound to H SP90.
Journal ArticleDOI
Protective effect of gedunin on TLR-mediated inflammation by modulation of inflammasome activation and cytokine production: Evidence of a multitarget compound
Perla Villani Borges,Katelim Hottz Moret,Nulgumnalli Manjunathaiah Raghavendra,Thadeu Estevam Moreira Maramaldo Costa,Ana Paula T. Monteiro,Alan Brito Carneiro,Patricia Pacheco,Jairo R. Temerozo,Dumith Chequer Bou-Habib,Maria das Graças Henriques,Carmen Penido +10 more
TL;DR: The data demonstrate that gedunin modulates TLR4, TLR3 and TLR2‐mediated responses and reveal new molecular targets for this compound, as well as demonstrating its modulatory effect on TLR activation in vitro and in vivo.
Journal ArticleDOI
hERG quality control and the long QT syndrome.
TL;DR: In this paper, the authors provide a background on the structure and cellular trafficking of hERG as well as inherited and acquired long-QT syndrome type-2 (LQT2) and introduce the more novel view that there is a significant peripheral QC at the PM and peripheral cellular compartments.
Journal ArticleDOI
Folding and Domain Interactions of Three Orthologs of Hsp90 Studied by Single-Molecule Force Spectroscopy
Markus Jahn,Katarzyna M. Tych,Hannah Girstmair,Maximilian Steinmaßl,Thorsten Hugel,Johannes Buchner,Matthias Rief +6 more
TL;DR: The domain interactions mediated by the charged linker, involved in the conformational cycles of all three orthologs, are much stronger for Grp94 than for Hsp82, keeping the N-terminal domain and the middle domain in close proximity.
References
More filters
Journal ArticleDOI
Protein S-nitrosylation: purview and parameters.
Douglas T. Hess,Akio Matsumoto,Sung Oog Kim,Harvey E. Marshall,Jonathan S. Stamler,Jonathan S. Stamler +5 more
TL;DR: S-nitrosylation conveys a large part of the ubiquitous influence of nitric oxide on cellular signal transduction, and provides a mechanism for redox-based physiological regulation.
Journal ArticleDOI
Steroid receptor interactions with heat shock protein and immunophilin chaperones.
William B. Pratt,David O. Toft +1 more
TL;DR: A historical perspective on a body of steroid receptor research dealing with the structure and physiological significance of the untransformed 9S receptor is provided, and it is shown that hsp90 itself exists in a variety of native multiprotein heterocomplexes independent of steroid receptors and other 'substrate' proteins.
Journal ArticleDOI
HSP90 at the hub of protein homeostasis: emerging mechanistic insights
TL;DR: Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions.
Journal ArticleDOI
Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery.
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.
Journal ArticleDOI
Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation.
TL;DR: It is demonstrated that HSP participation in multimolecular complex formation is required for src-mediated transformation and can provide a target for drug modulation.