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TitleSnapshots of actin and tubulin folding inside the TRiC chaperonin.
Journal, issue, pagesNat Struct Mol Biol, Vol. 29, Issue 5, Page 420-429, Year 2022
Publish dateApr 21, 2022
AuthorsJohn 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 AbstractThe 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 linksNat Struct Mol Biol / PubMed:35449234 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 3.5 Å
Structure data

EMDB-12605, PDB-7nvl:
Human TRiC complex in closed state with nanobody bound (Consensus Map)
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-12606, PDB-7nvm:
Human TRiC complex in closed state with nanobody Nb18, actin and PhLP2A bound
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-12607, PDB-7nvn:
Human TRiC complex in closed state with nanobody and tubulin bound
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-12608, PDB-7nvo:
Human TRiC complex in open state with nanobody bound
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-MG:
Unknown entry

ChemComp-AF3:
ALUMINUM FLUORIDE / Aluminium fluoride

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • lama glama (llama)
  • Human (human)
KeywordsCHAPERONE / TRiC / CCT / ATP hydrolysis / type II chaperonin / protein folding / Structural Genomics / Structural Genomics Consortium / SGC / actin / tubulin

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