+Open data
-Basic information
Entry | Database: PDB / ID: 7l7i | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of Hsp90:FKBP51:p23 closed-state complex | |||||||||
Components |
| |||||||||
Keywords | ISOMERASE/CHAPERONE / ISOMERASE-CHAPERONE complex | |||||||||
Function / homology | Function and homology information 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 / sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / prostaglandin biosynthetic process / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / skin development / protein insertion into mitochondrial outer membrane / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / 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 / chaperone cofactor-dependent protein refolding / regulation of protein ubiquitination / skeletal muscle contraction / protein unfolding / telomere maintenance via telomerase / HSF1-dependent transactivation / response to unfolded protein / positive regulation of cell size / chaperone-mediated protein complex assembly / regulation of protein-containing complex assembly / HSF1 activation / Attenuation phase / RHOBTB2 GTPase cycle / positive regulation of defense response to virus by host / eNOS activation / axonal growth cone / positive regulation of lamellipodium assembly / DNA polymerase binding / MECP2 regulates neuronal receptors and channels / activation of innate immune response / positive regulation of phosphorylation / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / chaperone-mediated protein folding / 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 / heat shock protein binding / response to salt stress / cardiac muscle cell apoptotic process / endocytic vesicle lumen / Recruitment of NuMA to mitotic centrosomes / positive regulation of cardiac muscle contraction / Anchoring of the basal body to the plasma membrane / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / telomere maintenance / nitric-oxide synthase regulator activity / positive regulation of interferon-beta production / response to cold / protein tyrosine kinase binding / lysosomal lumen / AURKA Activation by TPX2 / Constitutive Signaling by Overexpressed ERBB2 / ESR-mediated signaling / VEGFR2 mediated vascular permeability / response to cocaine / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / response to bacterium / ATP-dependent protein folding chaperone / brush border membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Lee, K. / Thwin, A.C. / Tse, E. / Gates, S.N. / Southworth, D.R. | |||||||||
Funding support | United States, 2items
| |||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7l7i.cif.gz | 318.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7l7i.ent.gz | 247.6 KB | Display | PDB format |
PDBx/mmJSON format | 7l7i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7l7i_validation.pdf.gz | 1001.7 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7l7i_full_validation.pdf.gz | 1004.8 KB | Display | |
Data in XML | 7l7i_validation.xml.gz | 47.8 KB | Display | |
Data in CIF | 7l7i_validation.cif.gz | 74.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l7/7l7i ftp://data.pdbj.org/pub/pdb/validation_reports/l7/7l7i | HTTPS FTP |
-Related structure data
Related structure data | 23213MC 7l7jC C: citing same article (ref.) M: map data used to model this data |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 51290.191 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FKBP5, AIG6, FKBP51 / Production host: Escherichia coli (E. coli) / References: UniProt: Q13451, peptidylprolyl isomerase | ||||||
---|---|---|---|---|---|---|---|
#2: Protein | Mass: 84781.727 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AA1, HSP90A, HSPC1, HSPCA / Production host: Escherichia coli (E. coli) / References: UniProt: P07900 #3: Protein | | Mass: 18720.395 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTGES3, P23, TEBP / Production host: Escherichia coli (E. coli) / References: UniProt: Q15185, prostaglandin-E synthase #4: Chemical | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Hsp90:FKBP51:p23 closed-state complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Microscopy | Model: FEI TITAN KRIOS | ||||||||||||
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM | ||||||||||||
Electron lens | Mode: BRIGHT FIELD | ||||||||||||
Image recording |
|
-Processing
EM software |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
Particle selection | Num. of particles selected: 576169 | ||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 121882 / Symmetry type: POINT |