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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23213 | |||||||||
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Title | Cryo-EM structure of Hsp90:FKBP51:p23 closed-state complex | |||||||||
![]() | Cryo-EM structure of Hsp90:FKBP51:p23 closed-state complex | |||||||||
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![]() | ISOMERASE-CHAPERONE complex | |||||||||
Function / homology | ![]() lung saccule development / prostaglandin-E synthase / prostaglandin-E synthase activity / telomerase activity / nuclear receptor-mediated glucocorticoid 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 / nuclear receptor-mediated glucocorticoid 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 / positive regulation of tau-protein kinase activity / 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 / UTP binding / sperm plasma membrane / skin development / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / protein insertion into mitochondrial outer membrane / Respiratory syncytial virus genome replication / Rho GDP-dissociation inhibitor binding / Uptake and function of diphtheria toxin / FK506 binding / 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 / Assembly and release of respiratory syncytial virus (RSV) virions / dendritic growth cone / : / regulation of postsynaptic membrane neurotransmitter receptor levels / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / chaperone cofactor-dependent protein refolding / skeletal muscle contraction / telomere maintenance via telomerase / HSF1-dependent transactivation / positive regulation of cell size / response to unfolded protein / protein unfolding / chaperone-mediated protein complex assembly / HSF1 activation / regulation of protein-containing complex assembly / Attenuation phase / RHOBTB2 GTPase cycle / eNOS activation / axonal growth cone / positive regulation of lamellipodium assembly / DNA polymerase binding / MECP2 regulates neuronal receptors and channels / positive regulation of phosphorylation / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / chaperone-mediated protein folding / positive regulation of defense response to virus by host / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Signaling by ERBB2 / cardiac muscle cell apoptotic process / endocytic vesicle lumen / Recruitment of NuMA to mitotic centrosomes / response to salt stress / positive regulation of cardiac muscle contraction / Anchoring of the basal body to the plasma membrane / heat shock protein binding / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / activation of innate immune response / nitric-oxide synthase regulator activity / positive regulation of interferon-beta production / telomere maintenance / response to cold / Constitutive Signaling by Overexpressed ERBB2 / AURKA Activation by TPX2 / lysosomal lumen / ESR-mediated signaling / protein tyrosine kinase binding / VEGFR2 mediated vascular permeability / response to cocaine / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / brush border membrane / ATP-dependent protein folding chaperone / Signaling by ERBB2 TMD/JMD mutants Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Lee K / Thwin AC | |||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 179.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.3 KB 14.3 KB | Display Display | ![]() |
Images | ![]() | 36.5 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7l7iMC ![]() 7l7jC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Cryo-EM structure of Hsp90:FKBP51:p23 closed-state complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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Sample components
-Entire : Hsp90:FKBP51:p23 closed-state complex
Entire | Name: Hsp90:FKBP51:p23 closed-state complex |
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Components |
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-Supramolecule #1: Hsp90:FKBP51:p23 closed-state complex
Supramolecule | Name: Hsp90:FKBP51:p23 closed-state complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Peptidyl-prolyl cis-trans isomerase FKBP5
Macromolecule | Name: Peptidyl-prolyl cis-trans isomerase FKBP5 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: peptidylprolyl isomerase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 51.290191 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MTTDEGAKNN EESPTATVAE QGEDITSKKD RGVLKIVKRV GNGEETPMIG DKVYVHYKGK LSNGKKFDSS HDRNEPFVFS LGKGQVIKA WDIGVATMKK GEICHLLCKP EYAYGSAGSL PKIPSNATLF FEIELLDFKG EDLFEDGGII RRTKRKGEGY S NPNEGATV ...String: MTTDEGAKNN EESPTATVAE QGEDITSKKD RGVLKIVKRV GNGEETPMIG DKVYVHYKGK LSNGKKFDSS HDRNEPFVFS LGKGQVIKA WDIGVATMKK GEICHLLCKP EYAYGSAGSL PKIPSNATLF FEIELLDFKG EDLFEDGGII RRTKRKGEGY S NPNEGATV EIHLEGRCGG RMFDCRDVAF TVGEGEDHDI PIGIDKALEK MQREEQCILY LGPRYGFGEA GKPKFGIEPN AE LIYEVTL KSFEKAKESW EMDTKEKLEQ AAIVKEKGTV YFKGGKYMQA VIQYGKIVSW LEMEYGLSEK ESKASESFLL AAF LNLAMC YLKLREYTKA VECCDKALGL DSANEKGLYR RGEAQLLMNE FESAKGDFEK VLEVNPQNKA ARLQISMCQK KAKE HNERD RRIYANMFKK FAEQDAKEEA NKAMGKKTSE GVTNEKGTDS QAMEEEKPEG HV UniProtKB: Peptidyl-prolyl cis-trans isomerase FKBP5 |
-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: ![]() |
Molecular weight | Theoretical: 84.781727 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 UniProtKB: Heat shock protein HSP 90-alpha |
-Macromolecule #3: Prostaglandin E synthase 3
Macromolecule | Name: Prostaglandin E synthase 3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: prostaglandin-E synthase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 18.720395 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MQPASAKWYD RRDYVFIEFC VEDSKDVNVN FEKSKLTFSC LGGSDNFKHL NEIDLFHCID PNDSKHKRTD RSILCCLRKG ESGQSWPRL TKERAKLNWL SVDFNNWKDW EDDSDEDMSN FDRFSEMMNN MGGDEDVDLP EVDGADDDSQ DSDDEKMPDL E UniProtKB: Prostaglandin E synthase 3 |
-Macromolecule #4: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER
Macromolecule | Name: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / type: ligand / ID: 4 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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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 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |