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| Title | Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller. |
|---|---|
| Journal, issue, pages | Mol Cell, Vol. 83, Issue 21, Page 3852-33868.e6, Year 2023 |
| Publish date | Nov 2, 2023 |
 Authors | Shuxin Wang / Mikaila I Sass / Yujin Kwon / W Grant Ludlam / Theresa M Smith / Ethan J Carter / Nathan E Gladden / Margot Riggi / Janet H Iwasa / Barry M Willardson / Peter S Shen /  |
| PubMed Abstract | The Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with β-propeller domains. Here, ...The Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with β-propeller domains. Here, we determine the structures of human CCT in complex with its accessory co-chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gβ, a component of Regulator of G protein Signaling (RGS) complexes. Cryoelectron microscopy (cryo-EM) and image processing reveal an ensemble of distinct snapshots that represent the folding trajectory of Gβ from an unfolded molten globule to a fully folded β-propeller. These structures reveal the mechanism by which CCT directs Gβ folding through initiating specific intermolecular contacts that facilitate the sequential folding of individual β sheets until the propeller closes into its native structure. This work directly visualizes chaperone-mediated protein folding and establishes that CCT orchestrates folding by stabilizing intermediates through interactions with surface residues that permit the hydrophobic core to coalesce into its folded state. |
 External links | Mol Cell / PubMed:37852256 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.7 - 3.7 Å |
| Structure data | EMDB-40439, PDB-8sfe: EMDB-40440, PDB-8sff: EMDB-40452, PDB-8sg8: EMDB-40453, PDB-8sg9: EMDB-40454, PDB-8sgc: EMDB-40461, PDB-8sgl: EMDB-40464, PDB-8sgq: EMDB-40481, PDB-8sh9: EMDB-40482, PDB-8sha: EMDB-40484, PDB-8shd: EMDB-40485, PDB-8she: EMDB-40486, PDB-8shf: EMDB-40487, PDB-8shg: EMDB-40488, PDB-8shl: EMDB-40489, PDB-8shn: EMDB-40490, PDB-8sho: EMDB-40491, PDB-8shp: EMDB-40492, PDB-8shq: EMDB-40494, PDB-8sht: |
| Chemicals |  ChemComp-ADP:  ChemComp-MG:  ChemComp-AF3:  ChemComp-HOH: |
| Source |
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 Keywords | CHAPERONE / CCT / Gb5 / complex / open |
homo sapiens (human)