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Yorodumi- EMDB-23054: Focused map of the Hsp90-Hsp70-Hop-GR complex: Hsp90B-NTD-MD:Hsp7... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23054 | |||||||||
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Title | Focused map of the Hsp90-Hsp70-Hop-GR complex: Hsp90B-NTD-MD:Hsp70D-NBD | |||||||||
Map data | Focused map of the Hsp90-Hsp70-Hop-GR complex: Hsp90B-NTD-MD:Hsp70D-NBD | |||||||||
Sample |
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Function / homology | Function and homology information positive regulation of endoribonuclease activity / denatured protein binding / cellular heat acclimation / negative regulation of inclusion body assembly / Viral RNP Complexes in the Host Cell Nucleus / positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway / death receptor agonist activity / C3HC4-type RING finger domain binding / ATP-dependent protein disaggregase activity / positive regulation of microtubule nucleation ...positive regulation of endoribonuclease activity / denatured protein binding / cellular heat acclimation / negative regulation of inclusion body assembly / Viral RNP Complexes in the Host Cell Nucleus / positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway / death receptor agonist activity / C3HC4-type RING finger domain binding / ATP-dependent protein disaggregase activity / positive regulation of microtubule nucleation / misfolded protein binding / regulation of mitotic spindle assembly / positive regulation of tumor necrosis factor-mediated signaling pathway / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / transcription regulator inhibitor activity / aggresome / lysosomal transport / sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / positive regulation of tau-protein kinase activity / protein insertion into mitochondrial outer membrane / telomerase holoenzyme complex assembly / chaperone-mediated autophagy / Rho GDP-dissociation inhibitor binding / cellular response to steroid hormone stimulus / Uptake and function of diphtheria toxin / mitochondrial transport / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / PIWI-interacting RNA (piRNA) biogenesis / TPR domain binding / mRNA catabolic process / non-chaperonin molecular chaperone ATPase / regulation of postsynaptic membrane neurotransmitter receptor levels / dendritic growth cone / chaperone cofactor-dependent protein refolding / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / positive regulation of cell size / skeletal muscle contraction / protein unfolding / regulation of protein-containing complex assembly / HSF1-dependent transactivation / telomere maintenance via telomerase / response to unfolded protein / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / Regulation of HSF1-mediated heat shock response / HSF1 activation / chaperone-mediated protein complex assembly / Attenuation phase / cellular response to unfolded protein / RHOBTB2 GTPase cycle / DNA polymerase binding / positive regulation of lamellipodium assembly / axonal growth cone / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / eNOS activation / inclusion body / ATP metabolic process / protein folding chaperone / endocytic vesicle lumen / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / negative regulation of protein ubiquitination / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / positive regulation of cardiac muscle contraction / positive regulation of defense response to virus by host / Signaling by ERBB2 / Recruitment of mitotic centrosome proteins and complexes / cardiac muscle cell apoptotic process / response to salt stress / positive regulation of telomerase activity / Recruitment of NuMA to mitotic centrosomes / heat shock protein binding / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / protein tyrosine kinase binding / Anchoring of the basal body to the plasma membrane / positive regulation of interferon-beta production / centriole / activation of innate immune response / response to cold / nitric-oxide synthase regulator activity / lysosomal lumen / Constitutive Signaling by Overexpressed ERBB2 / ESR-mediated signaling Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.53 Å | |||||||||
Authors | Wang RY / Agard DA | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2022 Title: Structure of Hsp90-Hsp70-Hop-GR reveals the Hsp90 client-loading mechanism. Authors: Ray Yu-Ruei Wang / Chari M Noddings / Elaine Kirschke / Alexander G Myasnikov / Jill L Johnson / David A Agard / Abstract: Maintaining a healthy proteome is fundamental for the survival of all organisms. Integral to this are Hsp90 and Hsp70, molecular chaperones that together facilitate the folding, remodelling and ...Maintaining a healthy proteome is fundamental for the survival of all organisms. Integral to this are Hsp90 and Hsp70, molecular chaperones that together facilitate the folding, remodelling and maturation of the many 'client proteins' of Hsp90. The glucocorticoid receptor (GR) is a model client protein that is strictly dependent on Hsp90 and Hsp70 for activity. Chaperoning GR involves a cycle of inactivation by Hsp70; formation of an inactive GR-Hsp90-Hsp70-Hop 'loading' complex; conversion to an active GR-Hsp90-p23 'maturation' complex; and subsequent GR release. However, to our knowledge, a molecular understanding of this intricate chaperone cycle is lacking for any client protein. Here we report the cryo-electron microscopy structure of the GR-loading complex, in which Hsp70 loads GR onto Hsp90, uncovering the molecular basis of direct coordination by Hsp90 and Hsp70. The structure reveals two Hsp70 proteins, one of which delivers GR and the other scaffolds the Hop cochaperone. Hop interacts with all components of the complex, including GR, and poises Hsp90 for subsequent ATP hydrolysis. GR is partially unfolded and recognized through an extended binding pocket composed of Hsp90, Hsp70 and Hop, revealing the mechanism of GR loading and inactivation. Together with the GR-maturation complex structure, we present a complete molecular mechanism of chaperone-dependent client remodelling, and establish general principles of client recognition, inhibition, transfer and activation. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23054.map.gz | 98 MB | EMDB map data format | |
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Header (meta data) | emd-23054-v30.xml emd-23054.xml | 10.1 KB 10.1 KB | Display Display | EMDB header |
Images | emd_23054.png | 151.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23054 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23054 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23054.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Focused map of the Hsp90-Hsp70-Hop-GR complex: Hsp90B-NTD-MD:Hsp70D-NBD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Hsp90-Hsp70-Hop-GR complex
Entire | Name: Hsp90-Hsp70-Hop-GR complex |
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Components |
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-Supramolecule #1: Hsp90-Hsp70-Hop-GR complex
Supramolecule | Name: Hsp90-Hsp70-Hop-GR complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 80.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.0) |
Final 3D classification | Number classes: 4 / Software - Name: RELION (ver. 3.0) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.0) |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.53 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 56945 |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 92 |
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