+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human TRiC-tubulin-S3 | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | STRUCTURAL PROTEIN | |||||||||
Function / homology | ![]() odontoblast differentiation / 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 / cytoskeleton-dependent intracellular transport / Folding of actin by CCT/TriC ...odontoblast differentiation / 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 / cytoskeleton-dependent intracellular transport / Folding of actin by CCT/TriC / binding of sperm to zona pellucida / positive regulation of telomerase RNA localization to Cajal body / Formation of tubulin folding intermediates by CCT/TriC / natural killer cell mediated cytotoxicity / Prefoldin mediated transfer of substrate to CCT/TriC / chaperonin-containing T-complex / GTPase activating protein binding / RHOBTB1 GTPase cycle / intermediate filament cytoskeleton / WD40-repeat domain binding / intercellular bridge / regulation of synapse organization / pericentriolar material / nuclear envelope lumen / beta-tubulin binding / MHC class I protein binding / Association of TriC/CCT with target proteins during biosynthesis / microtubule-based process / chaperone-mediated protein complex assembly / spindle assembly / RHOBTB2 GTPase cycle / heterochromatin / chaperone-mediated protein folding / protein folding chaperone / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / : / Recruitment of NuMA to mitotic centrosomes / positive regulation of telomere maintenance via telomerase / Anchoring of the basal body to the plasma membrane / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / AURKA Activation by TPX2 / acrosomal vesicle / mRNA 3'-UTR binding / cell projection / ATP-dependent protein folding chaperone / response to virus / structural constituent of cytoskeleton / mitotic spindle / mRNA 5'-UTR binding / cilium / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton organization / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G-protein beta-subunit binding / microtubule cytoskeleton / Regulation of PLK1 Activity at G2/M Transition / azurophil granule lumen / unfolded protein binding / melanosome / protein folding / mitotic cell cycle / cell body / secretory granule lumen / microtubule / ficolin-1-rich granule lumen / Potential therapeutics for SARS / cytoskeleton / protein stabilization / cadherin binding / membrane raft / protein domain specific binding / cell division / GTPase activity / centrosome / ubiquitin protein ligase binding / Neutrophil degranulation / protein-containing complex binding / GTP binding / structural molecule activity / Golgi apparatus / ATP hydrolysis activity / protein-containing complex / RNA binding / extracellular exosome / extracellular region / nucleoplasm / ATP binding / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Cong Y / Liu CX | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 8.7 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 23.6 KB 23.6 KB | Display Display | ![]() |
Images | ![]() | 109.8 KB | ||
Filedesc metadata | ![]() | 8.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 463.2 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 462.7 KB | Display | |
Data in XML | ![]() | 6.4 KB | Display | |
Data in CIF | ![]() | 7.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7x0sMC ![]() 7wz3C ![]() 7x0aC ![]() 7x0vC ![]() 7x3jC ![]() 7x3uC ![]() 7x6qC ![]() 7x7yC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.318 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-
Sample components
+Entire : Human TRiC-tubulin-S3
+Supramolecule #1: Human TRiC-tubulin-S3
+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: Tubulin beta chain
+Macromolecule #10: ADENOSINE-5'-DIPHOSPHATE
+Macromolecule #11: MAGNESIUM ION
+Macromolecule #12: ALUMINUM FLUORIDE
+Macromolecule #13: water
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.5 / Component - Concentration: 50.0 mM / Component - Formula: NaCl / Component - Name: sodium Chloride |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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 |
-
Image processing
Startup model | Type of model: OTHER |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 103406 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |