+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23214 | |||||||||
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Title | Cryo-EM structure of Hsp90:p23 closed-state complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information lung saccule development / prostaglandin-E synthase / prostaglandin-E synthase activity / telomerase activity / intracellular glucocorticoid receptor signaling pathway / Aryl hydrocarbon receptor signalling / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / cyclooxygenase pathway / telomerase holoenzyme complex / glycogen biosynthetic process ...lung saccule development / prostaglandin-E synthase / prostaglandin-E synthase activity / telomerase activity / intracellular glucocorticoid receptor signaling pathway / Aryl hydrocarbon receptor signalling / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / cyclooxygenase pathway / telomerase holoenzyme complex / glycogen biosynthetic process / protein folding chaperone complex / prostaglandin biosynthetic process / sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / skin development / 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 / Rho GDP-dissociation inhibitor binding / 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 / chaperone cofactor-dependent protein refolding / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / positive regulation of cell size / skeletal muscle contraction / protein unfolding / HSF1-dependent transactivation / telomere maintenance via telomerase / response to unfolded protein / HSF1 activation / chaperone-mediated protein complex assembly / regulation of protein-containing complex assembly / Attenuation phase / RHOBTB2 GTPase cycle / DNA polymerase binding / positive regulation of lamellipodium assembly / eNOS activation / axonal growth cone / positive regulation of phosphorylation / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / positive regulation of cardiac muscle contraction / Signaling by ERBB2 / cardiac muscle cell apoptotic process / Recruitment of mitotic centrosome proteins and complexes / positive regulation of telomerase activity / response to salt stress / positive regulation of defense response to virus by host / endocytic vesicle lumen / Recruitment of NuMA to mitotic centrosomes / protein tyrosine kinase binding / Anchoring of the basal body to the plasma membrane / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / activation of innate immune response / response to cold / telomere maintenance / positive regulation of interferon-beta production / nitric-oxide synthase regulator activity / lysosomal lumen / Constitutive Signaling by Overexpressed ERBB2 / AURKA Activation by TPX2 / ESR-mediated signaling / response to cocaine / VEGFR2 mediated vascular permeability / brush border membrane / ATP-dependent protein folding chaperone / Signaling by ERBB2 TMD/JMD mutants / neuron migration / Hsp90 protein binding / Constitutive Signaling by EGFRvIII / DDX58/IFIH1-mediated induction of interferon-alpha/beta / Signaling by ERBB2 ECD mutants / tau protein binding / Signaling by ERBB2 KD Mutants / Regulation of necroptotic cell death Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Lee K / Thwin AC / Tse E / Gates SN / Southworth DR | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Mol Cell / Year: 2021 Title: The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state. Authors: Kanghyun Lee / Aye C Thwin / Cory M Nadel / Eric Tse / Stephanie N Gates / Jason E Gestwicki / Daniel R Southworth / Abstract: The Hsp90 chaperone promotes folding and activation of hundreds of client proteins in the cell through an ATP-dependent conformational cycle guided by distinct cochaperone regulators. The FKBP51 ...The Hsp90 chaperone promotes folding and activation of hundreds of client proteins in the cell through an ATP-dependent conformational cycle guided by distinct cochaperone regulators. The FKBP51 immunophilin binds Hsp90 with its tetratricopeptide repeat (TPR) domain and catalyzes peptidyl-prolyl isomerase (PPIase) activity during folding of kinases, nuclear receptors, and tau. Here we determined the cryoelectron microscopy (cryo-EM) structure of the human Hsp90:FKBP51:p23 complex to 3.3 Å, which, together with mutagenesis and crosslinking analyses, reveals the basis for cochaperone binding to Hsp90 during client maturation. A helix extension in the TPR functions as a key recognition element, interacting across the Hsp90 C-terminal dimer interface presented in the closed, ATP conformation. The PPIase domain is positioned along the middle domain, adjacent to Hsp90 client binding sites, whereas a single p23 makes stabilizing interactions with the N-terminal dimer. With this architecture, FKBP51 is positioned to act on specific client residues presented during Hsp90-catalyzed remodeling. | |||||||||
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_23214.map.gz | 179.4 MB | EMDB map data format | |
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Header (meta data) | emd-23214-v30.xml emd-23214.xml | 13.3 KB 13.3 KB | Display Display | EMDB header |
Images | emd_23214.png | 27 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23214 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23214 | HTTPS FTP |
-Related structure data
Related structure data | 7l7jMC 7l7iC C: citing same article (ref.) M: atomic model generated by this map |
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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_23214.map.gz / Format: CCP4 / Size: 190.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 0.814 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:p23 closed-state complex
Entire | Name: Hsp90:p23 closed-state complex |
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Components |
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-Supramolecule #1: Hsp90:p23 closed-state complex
Supramolecule | Name: Hsp90:p23 closed-state complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Macromolecule #1: Prostaglandin E synthase 3
Macromolecule | Name: Prostaglandin E synthase 3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: prostaglandin-E synthase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 18.720395 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MQPASAKWYD RRDYVFIEFC VEDSKDVNVN FEKSKLTFSC LGGSDNFKHL NEIDLFHCID PNDSKHKRTD RSILCCLRKG ESGQSWPRL TKERAKLNWL SVDFNNWKDW EDDSDEDMSN FDRFSEMMNN MGGDEDVDLP EVDGADDDSQ DSDDEKMPDL E |
-Macromolecule #2: Heat shock protein HSP 90-alpha
Macromolecule | Name: Heat shock protein HSP 90-alpha / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 84.781727 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR YESLTDPSKL DSGKELHINL IPNKQDRTL TIVDTGIGMT KADLINNLGT IAKSGTKAFM EALQAGADIS MIGQFGVGFY SAYLVAEKVT VITKHNDDEQ Y AWESSAGG ...String: MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR YESLTDPSKL DSGKELHINL IPNKQDRTL TIVDTGIGMT KADLINNLGT IAKSGTKAFM EALQAGADIS MIGQFGVGFY SAYLVAEKVT VITKHNDDEQ Y AWESSAGG SFTVRTDTGE PMGRGTKVIL HLKEDQTEYL EERRIKEIVK KHSQFIGYPI TLFVEKERDK EVSDDEAEEK ED KEEEKEK EEKESEDKPE IEDVGSDEEE EKKDGDKKKK KKIKEKYIDQ EELNKTKPIW TRNPDDITNE EYGEFYKSLT NDW EDHLAV KHFSVEGQLE FRALLFVPRR APFDLFENRK KKNNIKLYVR RVFIMDNCEE LIPEYLNFIR GVVDSEDLPL NISR EMLQQ SKILKVIRKN LVKKCLELFT ELAEDKENYK KFYEQFSKNI KLGIHEDSQN RKKLSELLRY YTSASGDEMV SLKDY CTRM KENQKHIYYI TGETKDQVAN SAFVERLRKH GLEVIYMIEP IDEYCVQQLK EFEGKTLVSV TKEGLELPED EEEKKK QEE KKTKFENLCK IMKDILEKKV EKVVVSNRLV TSPCCIVTST YGWTANMERI MKAQALRDNS TMGYMAAKKH LEINPDH SI IETLRQKAEA DKNDKSVKDL VILLYETALL SSGFSLEDPQ THANRIYRMI KLGLGIDEDD PTADDTSAAV TEEMPPLE G DDDTSRMEEV D |
-Macromolecule #3: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER
Macromolecule | Name: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / type: ligand / ID: 3 / Number of copies: 2 / Formula: ANP |
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Molecular weight | Theoretical: 506.196 Da |
Chemical component information | ChemComp-ANP: |
-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 |
-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 | #0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #0 - Average electron dose: 70.0 e/Å2 / #1 - Image recording ID: 2 / #1 - Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / #1 - Average electron dose: 66.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 576169 |
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CTF correction | Software - Name: cryoSPARC (ver. 2) |
Startup model | #0 - Type of model: PDB ENTRY #0 - PDB model - PDB ID: #1 - Type of model: PDB ENTRY #1 - PDB model - PDB ID: |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2) / Number images used: 239079 |
Image recording ID | 1 |