|Entry||Database: PDB / ID: 6ahf|
|Title||CryoEM Reconstruction of Hsp104 N728A Hexamer|
|Components||Heat shock protein 104Heat shock response|
|Keywords||CHAPERONE / chaperone / Hsp / holdase|
|Function / homology||AAA lid domain / ClpA/B family / Chaperonins clpA/B signature 2. / Chaperonins clpA/B signature 1. / C-terminal, D2-small domain, of ClpB protein / AAA domain (Cdc48 subfamily) / Clp amino terminal domain, pathogenicity island component / ATPase family associated with various cellular activities (AAA) / Clp, N-terminal domain superfamily / ClpA/B, conserved site 2 ...AAA lid domain / ClpA/B family / Chaperonins clpA/B signature 2. / Chaperonins clpA/B signature 1. / C-terminal, D2-small domain, of ClpB protein / AAA domain (Cdc48 subfamily) / Clp amino terminal domain, pathogenicity island component / ATPase family associated with various cellular activities (AAA) / Clp, N-terminal domain superfamily / ClpA/B, conserved site 2 / P-loop containing nucleoside triphosphate hydrolase / Clp ATPase, C-terminal / ClpA/B, conserved site 1 / Clp, N-terminal / ATPase, AAA-type, core / AAA+ ATPase domain / inheritance of oxidatively modified proteins involved in replicative cell aging / trehalose metabolism in response to heat stress / TRC complex / cellular heat acclimation / protein folding in endoplasmic reticulum / stress granule disassembly / protein metabolic process / chaperone cofactor-dependent protein refolding / protein unfolding / nuclear periphery / ADP binding / ATPase activity, coupled / unfolded protein binding / chaperone binding / ATP binding / identical protein binding / nucleus / cytoplasm / Heat shock protein 104|
Function and homology information
|Specimen source||Saccharomyces cerevisiae S288c (yeast)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 6.78 Å resolution|
|Authors||Zhang, X. / Zhang, L. / Zhang, S.|
|Citation||Journal: J. Biol. Chem. / Year: 2019|
Title: Heat shock protein 104 (HSP104) chaperones soluble Tau via a mechanism distinct from its disaggregase activity.
Authors: Xiang Zhang / Shengnan Zhang / Li Zhang / Jinxia Lu / Chunyu Zhao / Feng Luo / Dan Li / Xueming Li / Cong Liu
Abstract: Heat shock protein 104 (HSP104) is a conserved AAA+ protein disaggregase, can disassemble the toxic aggregates formed by different amyloid proteins, and is protective in various animal models ...Heat shock protein 104 (HSP104) is a conserved AAA+ protein disaggregase, can disassemble the toxic aggregates formed by different amyloid proteins, and is protective in various animal models associated with amyloid-related diseases. Extensive studies have attempted to elucidate how HSP104 disassembles the aggregated form of clients. Here, we found that HSP104 exhibits a potent holdase activity that does not require energy, prevents the soluble form of amyloid clients from aggregating, and differs from HSP104's disaggregase activity. Using cryo-EM, NMR and additional biophysical approaches, we found that HSP104 utilizes its small subdomain of nucleotide-binding domain 2 (ssNBD2) to capture the soluble amyloid client (K19 of Tau) independent of its ATP hydrolysis activity. Our results indicate that HSP104 utilizes two fundamental distinct mechanisms to chaperone different forms of amyloid client and highlight the important yet previously unappreciated function of ssNBD2 in chaperoning amyloid client and thereby preventing pathological aggregation.
SummaryFull reportAbout validation report
|Date||Deposition: Aug 17, 2018 / Release: Feb 13, 2019|
|Structure viewer||Molecule: |
Downloads & links
A: Heat shock protein 104
B: Heat shock protein 104
C: Heat shock protein 104
D: Heat shock protein 104
E: Heat shock protein 104
F: Heat shock protein 104
Mass: 102130.938 Da / Num. of mol.: 6 / Mutation: N728A / Source: (gene. exp.) Saccharomyces cerevisiae S288c (yeast) / Gene: HSP104 / Production host: Escherichia coli (E. coli) / References: UniProt: P31539
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: CryoEM Reconstruction of Hsp104 N728A Hexamer / Type: COMPLEX / Entity ID: 1 / Source: RECOMBINANT|
|Source (natural)||Organism: Saccharomyces cerevisiae S288c (yeast)|
|Source (recombinant)||Organism: Escherichia coli (E. coli)|
|Buffer solution||pH: 7.4|
|Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Specimen support||Grid material: COPPER / Grid type: Quantifoil R1.2/1.3|
|Vitrification||Cryogen name: ETHANE / Humidity: 100 %|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER|
|Electron lens||Mode: OTHER|
|Specimen holder||Cryogen: NITROGEN|
|Image recording||Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|Software||Name: PHENIX / Version: 1.10_2155: / Classification: refinement|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|3D reconstruction||Resolution: 6.78 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 69537 / Symmetry type: POINT|
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