+Open data
-Basic information
Entry | Database: PDB / ID: 8eoa | ||||||
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Title | Cryo-EM structure of human HSP90B-AIPL1 complex | ||||||
Components |
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Keywords | CHAPERONE / HSP90B / AIPL1 / phosphodiesterase 6 | ||||||
Function / homology | Function and homology information farnesylated protein binding / receptor ligand inhibitor activity / HSP90-CDC37 chaperone complex / regulation of opsin-mediated signaling pathway / negative regulation of proteasomal protein catabolic process / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / dynein axonemal particle / histone methyltransferase binding / phototransduction, visible light ...farnesylated protein binding / receptor ligand inhibitor activity / HSP90-CDC37 chaperone complex / regulation of opsin-mediated signaling pathway / negative regulation of proteasomal protein catabolic process / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / dynein axonemal particle / histone methyltransferase binding / phototransduction, visible light / positive regulation of protein localization to cell surface / ATP-dependent protein binding / protein kinase regulator activity / retina homeostasis / protein folding chaperone complex / telomerase holoenzyme complex assembly / Respiratory syncytial virus genome replication / Uptake and function of diphtheria toxin / TPR domain binding / Assembly and release of respiratory syncytial virus (RSV) virions / positive regulation of transforming growth factor beta receptor signaling pathway / dendritic growth cone / : / The NLRP3 inflammasome / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / telomere maintenance via telomerase / HSF1-dependent transactivation / response to unfolded protein / chaperone-mediated protein complex assembly / HSF1 activation / Attenuation phase / RHOBTB2 GTPase cycle / Purinergic signaling in leishmaniasis infection / cellular response to interleukin-4 / axonal growth cone / DNA polymerase binding / supramolecular fiber organization / chaperone-mediated protein folding / heat shock protein binding / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / protein folding chaperone / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / nitric-oxide synthase regulator activity / photoreceptor inner segment / ESR-mediated signaling / peptidyl-prolyl cis-trans isomerase activity / positive regulation of cell differentiation / ATP-dependent protein folding chaperone / peptide binding / DDX58/IFIH1-mediated induction of interferon-alpha/beta / placenta development / tau protein binding / kinase binding / Regulation of actin dynamics for phagocytic cup formation / histone deacetylase binding / Chaperone Mediated Autophagy / The role of GTSE1 in G2/M progression after G2 checkpoint / disordered domain specific binding / double-stranded RNA binding / positive regulation of nitric oxide biosynthetic process / unfolded protein binding / melanosome / protein folding / MHC class II protein complex binding / regulation of protein localization / cellular response to heat / secretory granule lumen / Estrogen-dependent gene expression / ficolin-1-rich granule lumen / Potential therapeutics for SARS / protein dimerization activity / regulation of cell cycle / protein stabilization / nuclear speck / cadherin binding / neuronal cell body / ubiquitin protein ligase binding / Neutrophil degranulation / negative regulation of apoptotic process / virion attachment to host cell / apoptotic process / protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / perinuclear region of cytoplasm / cell surface / protein homodimerization activity / ATP hydrolysis activity / protein-containing complex / mitochondrion / RNA binding / extracellular exosome / extracellular region / nucleoplasm / ATP binding / identical protein binding / membrane / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||
Authors | Srivastava, D. / Artemyev, N.O. | ||||||
Funding support | United States, 1items
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Citation | Journal: Structure / Year: 2023 Title: Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1. Authors: Dhiraj Srivastava / Ravi P Yadav / Sneha Singh / Kimberly Boyd / Nikolai O Artemyev / Abstract: Photoreceptor phosphodiesterase PDE6 is central for visual signal transduction. Maturation of PDE6 depends on a specialized chaperone complex of HSP90 with aryl hydrocarbon receptor-interacting ...Photoreceptor phosphodiesterase PDE6 is central for visual signal transduction. Maturation of PDE6 depends on a specialized chaperone complex of HSP90 with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1). Disruption of PDE6 maturation underlies a severe form of retina degeneration. Here, we report a 3.9 Å cryoelectron microscopy (cryo-EM) structure of the complex of HSP90 with AIPL1. This structure reveals a unique interaction of the FK506-binding protein (FKBP)-like domain of AIPL1 with HSP90 at its dimer interface. Unusually, the N terminus AIPL1 inserts into the HSP90 lumen in a manner that was observed previously for HSP90 clients. Deletion of the 7 N-terminal residues of AIPL1 decreased its ability to cochaperone PDE6. Multi-body refinement of the cryo-EM data indicated large swing-like movements of AIPL1-FKBP. Modeling the complex of HSP90 with AIPL1 using crosslinking constraints indicated proximity of the mobile tetratricopeptide repeat (TPR) domain with the C-terminal domain of HSP90. Our study establishes a framework for future structural studies of PDE6 maturation. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8eoa.cif.gz | 298.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8eoa.ent.gz | 232.8 KB | Display | PDB format |
PDBx/mmJSON format | 8eoa.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8eoa_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8eoa_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 8eoa_validation.xml.gz | 126.7 KB | Display | |
Data in CIF | 8eoa_validation.cif.gz | 233.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/eo/8eoa ftp://data.pdbj.org/pub/pdb/validation_reports/eo/8eoa | HTTPS FTP |
-Related structure data
Related structure data | 28332MC 8eobC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 87170.227 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AB1, HSP90B, HSPC2, HSPCB / Production host: Escherichia coli (E. coli) / Strain (production host): rosetta 2 (DE3) / References: UniProt: P08238 #2: Protein | | Mass: 40763.543 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Aipl1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q924K1 #3: Chemical | #4: Chemical | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: HSP90B/AIPL1 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT | ||||||||||||||||
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Molecular weight | Value: 0.215 MDa / Experimental value: NO | ||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||
Source (recombinant) | Organism: Escherichia coli (E. coli) / Strain: Rosetta 2 (DE3) | ||||||||||||||||
Buffer solution | pH: 7.5 / Details: 25 mM HEPES, 200 mM NaCl, 1 mM TCEP, pH 7.5 | ||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/1 | ||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 900 nm |
Image recording | Average exposure time: 0.032 sec. / Electron dose: 1.5 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 443532 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 81152 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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