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Open data
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Basic information
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Title | cryo-EM structure of human TRiC-ADP-AlFx | |||||||||
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![]() | Human TRiC / tubulin / STRUCTURAL PROTEIN | |||||||||
Function / homology | ![]() zona pellucida receptor complex / scaRNA localization to Cajal body / chaperone mediated protein folding independent of cofactor / positive regulation of establishment of protein localization to telomere / positive regulation of protein localization to Cajal body / tubulin complex assembly / BBSome-mediated cargo-targeting to cilium / binding of sperm to zona pellucida / Folding of actin by CCT/TriC / Formation of tubulin folding intermediates by CCT/TriC ...zona pellucida receptor complex / scaRNA localization to Cajal body / chaperone mediated protein folding independent of cofactor / positive regulation of establishment of protein localization to telomere / positive regulation of protein localization to Cajal body / tubulin complex assembly / BBSome-mediated cargo-targeting to cilium / binding of sperm to zona pellucida / Folding of actin by CCT/TriC / Formation of tubulin folding intermediates by CCT/TriC / positive regulation of telomerase RNA localization to Cajal body / chaperonin-containing T-complex / Prefoldin mediated transfer of substrate to CCT/TriC / RHOBTB1 GTPase cycle / intermediate filament cytoskeleton / WD40-repeat domain binding / pericentriolar material / beta-tubulin binding / Association of TriC/CCT with target proteins during biosynthesis / : / chaperone-mediated protein complex assembly / RHOBTB2 GTPase cycle / heterochromatin / chaperone-mediated protein folding / protein folding chaperone / positive regulation of telomere maintenance via telomerase / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / acrosomal vesicle / cell projection / mRNA 3'-UTR binding / ATP-dependent protein folding chaperone / response to virus / cilium / mRNA 5'-UTR binding / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G-protein beta-subunit binding / azurophil granule lumen / unfolded protein binding / melanosome / protein folding / cell body / secretory granule lumen / ficolin-1-rich granule lumen / microtubule / cytoskeleton / protein stabilization / cadherin binding / centrosome / ubiquitin protein ligase binding / Neutrophil degranulation / Golgi apparatus / ATP hydrolysis activity / RNA binding / extracellular exosome / extracellular region / nucleoplasm / ATP binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Cong Y / Liu CX | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM. Authors: Caixuan Liu / Mingliang Jin / Shutian Wang / Wenyu Han / Qiaoyu Zhao / Yifan Wang / Cong Xu / Lei Diao / Yue Yin / Chao Peng / Lan Bao / Yanxing Wang / Yao Cong / ![]() Abstract: The eukaryotic chaperonin TRiC/CCT assists the folding of about 10% of cytosolic proteins through an ATP-driven conformational cycle, and the essential cytoskeleton protein tubulin is the obligate ...The eukaryotic chaperonin TRiC/CCT assists the folding of about 10% of cytosolic proteins through an ATP-driven conformational cycle, and the essential cytoskeleton protein tubulin is the obligate substrate of TRiC. Here, we present an ensemble of cryo-EM structures of endogenous human TRiC throughout its ATPase cycle, with three of them revealing endogenously engaged tubulin in different folding stages. The open-state TRiC-tubulin-S1 and -S2 maps show extra density corresponding to tubulin in the cis-ring chamber of TRiC. Our structural and XL-MS analyses suggest a gradual upward translocation and stabilization of tubulin within the TRiC chamber accompanying TRiC ring closure. In the closed TRiC-tubulin-S3 map, we capture a near-natively folded tubulin-with the tubulin engaging through its N and C domains mainly with the A and I domains of the CCT3/6/8 subunits through electrostatic and hydrophilic interactions. Moreover, we also show the potential role of TRiC C-terminal tails in substrate stabilization and folding. Our study delineates the pathway and molecular mechanism of TRiC-mediated folding of tubulin along the ATPase cycle of TRiC, and may also inform the design of therapeutic agents targeting TRiC-tubulin interactions. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 10.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.2 KB 22.2 KB | Display Display | ![]() |
Images | ![]() | 110.2 KB | ||
Filedesc metadata | ![]() | 8.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7x0vMC ![]() 7wz3C ![]() 7x0aC ![]() 7x0sC ![]() 7x3jC ![]() 7x3uC ![]() 7x6qC ![]() 7x7yC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Voxel size | X=Y=Z: 1.318 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Human TRiC-ADP-AlFx
+Supramolecule #1: Human TRiC-ADP-AlFx
+Macromolecule #1: T-complex protein 1 subunit zeta
+Macromolecule #2: T-complex protein 1 subunit theta
+Macromolecule #3: T-complex protein 1 subunit eta
+Macromolecule #4: T-complex protein 1 subunit gamma
+Macromolecule #5: T-complex protein 1 subunit epsilon
+Macromolecule #6: T-complex protein 1 subunit delta
+Macromolecule #7: T-complex protein 1 subunit beta
+Macromolecule #8: T-complex protein 1 subunit alpha
+Macromolecule #9: ADENOSINE-5'-DIPHOSPHATE
+Macromolecule #10: MAGNESIUM ION
+Macromolecule #11: ALUMINUM FLUORIDE
+Macromolecule #12: water
-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 / Component - Concentration: 50.0 mM / Component - Formula: NaCl / Component - Name: sodium Chloride |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 38.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 62412 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |