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-Structure paper
Title | Snapshots of actin and tubulin folding inside the TRiC chaperonin. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 29, Issue 5, Page 420-429, Year 2022 |
Publish date | Apr 21, 2022 |
Authors | John J Kelly / Dale Tranter / Els Pardon / Gamma Chi / Holger Kramer / Lotta Happonen / Kelly M Knee / Jay M Janz / Jan Steyaert / Christine Bulawa / Ville O Paavilainen / Juha T Huiskonen / Wyatt W Yue / |
PubMed Abstract | The integrity of a cell's proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, ...The integrity of a cell's proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC. |
External links | Nat Struct Mol Biol / PubMed:35449234 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.5 - 3.5 Å |
Structure data | EMDB-12605, PDB-7nvl: EMDB-12606, PDB-7nvm: EMDB-12607, PDB-7nvn: EMDB-12608, PDB-7nvo: |
Chemicals | ChemComp-ADP: ChemComp-MG: ChemComp-AF3: ChemComp-HOH: |
Source |
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Keywords | CHAPERONE / TRiC / CCT / ATP hydrolysis / type II chaperonin / protein folding / Structural Genomics / Structural Genomics Consortium / SGC / actin / tubulin |