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Structural visualization of the tubulin folding pathway directed by human chaperonin TRiC/CCT.

Gestaut D, Zhao Y, Park J, Ma B, Leitner A, Collier M, Pintilie G, Roh SH, Chiu W, Frydman J
Cell 185 4770-4787.e20 (2022)
Related entries: 7ttn, 7ttt, 7tub, 7wu7

Cited: 14 times
EuropePMC logo PMID: 36493755

Abstract

The ATP-dependent ring-shaped chaperonin TRiC/CCT is essential for cellular proteostasis. To uncover why some eukaryotic proteins can only fold with TRiC assistance, we reconstituted the folding of β-tubulin using human prefoldin and TRiC. We find unstructured β-tubulin is delivered by prefoldin to the open TRiC chamber followed by ATP-dependent chamber closure. Cryo-EM resolves four near-atomic-resolution structures containing progressively folded β-tubulin intermediates within the closed TRiC chamber, culminating in native tubulin. This substrate folding pathway appears closely guided by site-specific interactions with conserved regions in the TRiC chamber. Initial electrostatic interactions between the TRiC interior wall and both the folded tubulin N domain and its C-terminal E-hook tail establish the native substrate topology, thus enabling C-domain folding. Intrinsically disordered CCT C termini within the chamber promote subsequent folding of tubulin's core and middle domains and GTP-binding. Thus, TRiC's chamber provides chemical and topological directives that shape the folding landscape of its obligate substrates.

Articles - 7trg mentioned but not cited (1)

  1. Structural visualization of the tubulin folding pathway directed by human chaperonin TRiC/CCT. Gestaut D, Zhao Y, Park J, Ma B, Leitner A, Collier M, Pintilie G, Roh SH, Chiu W, Frydman J. Cell 185 4770-4787.e20 (2022)


Reviews citing this publication (5)

  1. Mechanisms and pathology of protein misfolding and aggregation. Louros N, Schymkowitz J, Rousseau F. Nat Rev Mol Cell Biol 24 912-933 (2023)
  2. Balancing Act: Tubulin Glutamylation and Microtubule Dynamics in Toxoplasma gondii. Delgado ILS, Gonçalves J, Fernandes R, Zúquete S, Basto AP, Leitão A, Soares H, Nolasco S. Microorganisms 12 488 (2024)
  3. Bridging structural and cell biology with cryo-electron microscopy. Nogales E, Mahamid J. Nature 628 47-56 (2024)
  4. In-Cell Dynamics: The Next Focus of All-Atom Simulations. Samuel Russell PP, Alaeen S, Pogorelov TV. J Phys Chem B 127 9863-9872 (2023)
  5. The role of molecular chaperone CCT/TRiC in translation elongation: A literature review. Que Y, Qiu Y, Ding Z, Zhang S, Wei R, Xia J, Lin Y. Heliyon 10 e29029 (2024)

Articles citing this publication (8)

  1. Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM. Liu C, Jin M, Wang S, Han W, Zhao Q, Wang Y, Xu C, Diao L, Yin Y, Peng C, Peng C, Bao L, Wang Y, Cong Y. Commun Biol 6 531 (2023)
  2. Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT. Han W, Jin M, Liu C, Zhao Q, Wang S, Wang Y, Yin Y, Peng C, Wang Y, Cong Y. Sci Adv 9 eade1207 (2023)
  3. A structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle. Park J, Kim H, Gestaut D, Lim S, Opoku-Nsiah KA, Leitner A, Frydman J, Roh SH. Nat Commun 15 1007 (2024)
  4. In silico protein dynamics in the human cytoplasm: Partial folding, misfolding, fold switching, and non-native interactions. Russell PPS, Rickard MM, Boob M, Gruebele M, Pogorelov TV. Protein Sci 32 e4790 (2023)
  5. Molecular Dynamics Mappings of the CCT/TRiC Complex-Mediated Protein Folding Cycle Using Diffracted X-ray Tracking. Araki K, Watanabe-Nakayama T, Sasaki D, Sasaki YC, Mio K. Int J Mol Sci 24 14850 (2023)
  6. STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation. Chen Y, Luo M, Tu H, Qi Y, Guo Y, Zhang X, Cui Y, Gao M, Zhou X, Zhu T, Zhu H, Situ C, Li Y, Guo X. Nat Commun 15 44 (2024)
  7. Single-cell expression predicts neuron-specific protein homeostasis networks. Pechmann S. Open Biol 14 230386 (2024)
  8. Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller. Wang S, Sass MI, Kwon Y, Ludlam WG, Smith TM, Carter EJ, Gladden NE, Riggi M, Iwasa JH, Willardson BM, Shen PS. Mol Cell 83 3852-3868.e6 (2023)


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