+検索条件
-Structure paper
タイトル | Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM. |
---|---|
ジャーナル・号・ページ | Commun Biol, Vol. 6, Issue 1, Page 531, Year 2023 |
掲載日 | 2023年5月16日 |
著者 | 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 / |
PubMed 要旨 | 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. |
リンク | Commun Biol / PubMed:37193829 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 - 4.5 Å |
構造データ | EMDB-32903, PDB-7wz3: EMDB-32922, PDB-7x0a: EMDB-32923, PDB-7x0s: EMDB-32926, PDB-7x0v: EMDB-32989, PDB-7x3j: EMDB-32993, PDB-7x3u: EMDB-33025, PDB-7x6q: EMDB-33053, PDB-7x7y: |
化合物 | ChemComp-ADP: ChemComp-MG: ChemComp-AF3: ChemComp-HOH: ChemComp-ATP: |
由来 |
|
キーワード | STRUCTURAL PROTEIN / tubulin / Human TRiC |