+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23050 | |||||||||
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Title | Atomic cryoEM structure of Hsp90-Hsp70-Hop-GR | |||||||||
Map data | Raw (unsharpened) map from Relion's refine3d. | |||||||||
Sample |
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Keywords | Client-loading / CHAPERONE | |||||||||
Function / homology | Function and homology information positive regulation of endoribonuclease activity / denatured protein binding / Regulation of NPAS4 gene transcription / cellular heat acclimation / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / death receptor agonist activity / 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 ...positive regulation of endoribonuclease activity / denatured protein binding / Regulation of NPAS4 gene transcription / cellular heat acclimation / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / death receptor agonist activity / 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 / C3HC4-type RING finger domain binding / dynein axonemal particle / steroid hormone binding / PTK6 Expression / ATP-dependent protein disaggregase activity / positive regulation of microtubule nucleation / neuroinflammatory response / glucocorticoid metabolic process / microglia differentiation / mammary gland duct morphogenesis / misfolded protein binding / maternal behavior / regulation of mitotic spindle assembly / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of tumor necrosis factor-mediated signaling pathway / astrocyte differentiation / cellular response to interleukin-7 / protein folding chaperone complex / transcription regulator inhibitor activity / cellular response to glucocorticoid stimulus / aggresome / RND1 GTPase cycle / motor behavior / 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 / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / regulation of gluconeogenesis / adrenal gland development / 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 / non-chaperonin molecular chaperone ATPase / regulation of postsynaptic membrane neurotransmitter receptor levels / dendritic growth cone / mRNA catabolic process / chaperone cofactor-dependent protein refolding / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / skeletal muscle contraction / positive regulation of cell size / HSF1-dependent transactivation / response to unfolded protein / telomere maintenance via telomerase / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / chaperone-mediated protein complex assembly / Regulation of HSF1-mediated heat shock response / protein unfolding / HSF1 activation / regulation of protein-containing complex assembly / Attenuation phase / cellular response to unfolded protein / estrogen response element binding / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / RHOBTB2 GTPase cycle / positive regulation of lamellipodium assembly / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / eNOS activation / axonal growth cone / DNA polymerase binding / nuclear receptor-mediated steroid hormone signaling pathway / protein folding chaperone / core promoter sequence-specific DNA binding / ATP metabolic process / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / inclusion body / Loss of Nlp from mitotic centrosomes Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.57 Å | |||||||||
Authors | Wang RY / Noddings CM | |||||||||
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_23050.map.gz | 97.9 MB | EMDB map data format | |
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Header (meta data) | emd-23050-v30.xml emd-23050.xml | 22.6 KB 22.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23050_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_23050.png | 77.7 KB | ||
Filedesc metadata | emd-23050.cif.gz | 7.3 KB | ||
Others | emd_23050_half_map_1.map.gz emd_23050_half_map_2.map.gz | 98.3 MB 98.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23050 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23050 | HTTPS FTP |
-Validation report
Summary document | emd_23050_validation.pdf.gz | 886.4 KB | Display | EMDB validaton report |
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Full document | emd_23050_full_validation.pdf.gz | 885.9 KB | Display | |
Data in XML | emd_23050_validation.xml.gz | 18.6 KB | Display | |
Data in CIF | emd_23050_validation.cif.gz | 24.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23050 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23050 | HTTPS FTP |
-Related structure data
Related structure data | 7kw7MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar 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_23050.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Raw (unsharpened) map from Relion's refine3d. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Half map: Unfiltered half1 map from Relion's refine3d.
File | emd_23050_half_map_1.map | ||||||||||||
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Annotation | Unfiltered half1 map from Relion's refine3d. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Unfiltered half2 map from Relion's refine3d.
File | emd_23050_half_map_2.map | ||||||||||||
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Annotation | Unfiltered half2 map from Relion's refine3d. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Hsp90-Hsp70-Hop-GR complex
+Supramolecule #1: Hsp90-Hsp70-Hop-GR complex
+Supramolecule #2: Heat shock protein HSP 90-alpha
+Supramolecule #3: Heat shock 70 kDa protein 1A
+Supramolecule #4: Stress-induced-phosphoprotein 1
+Supramolecule #5: Glucocorticoid receptor
+Macromolecule #1: Heat shock protein HSP 90-alpha
+Macromolecule #2: Heat shock 70 kDa protein 1A
+Macromolecule #3: Stress-induced-phosphoprotein 1
+Macromolecule #4: Glucocorticoid receptor
+Macromolecule #5: ADENOSINE-5'-DIPHOSPHATE
+Macromolecule #6: MAGNESIUM ION
+Macromolecule #7: POTASSIUM ION
-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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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 80 |
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Output model | PDB-7kw7: |