In preview of the a paper that appears in December 8, 2022 issue of Cell from Judith Frydman's group at Stanford, MCDB's James C.A. Bardwell references the Chamber of Secrets from the Harry Potter series when describing the hollow chamber of the chaperonin TRiC and how it facilitates protein folding.
"Unlike Hogwart’s original Chamber of Secrets, which merely acts to confine a dangerous snake-like basilisk, the TRiC chamber does something far more wonderous; it transforms a disordered snake-like chain of amino acids into tubulin, a highly ordered protein that is essential for cellular transport. It is as if slithering snakes are fed into TRiC’s magic chamber, and a functional transport protein comes flying out like a car.
The protein tasked with feeding proteins to TRiC is prefoldin, a tentacled protein that grips its substrate protein a bit like how an octopus would grab a sea snake. Prefoldin maintains tubulin in an unfolded configuration and then, by thrusting at least one of its tentacles into the chamber, manages to deposit the wiggling tubulin peptide chain into TRiC’s interior cavity. Disordered worm-like loops protruding from each TriC subunit become ordered upon ATP hydrolysis, and the lid to the chamber ominously snaps shut. In their tour de force, Gestaut et al. define tubulin-folding intermediates that are present within TRiC at near-atomic resolution, and, using a powerful combination of crosslinking mass spectrometry and cryoelectron microscopy (cryo-EM), they then help define the roles that individual domains of TRiC’s subunits play in tubulin folding."
Bardwell points out that protein folding in the cell relies heavily on chaperones. Much has been learned about chaperones, but visualizing how the substrate protein's structure changes while is is undergoing chaperone-mediated folding has been difficult.
The Cell paper provides a detailed structural view of the TRiC. The Bardwell Lab has used a crystallographic approach to visualize Spy folding Im7. [See: Protein folding on chaperone caught on video]
James C.A. Bardwell
Cell, Volume 185, Issue 25,2022, Pages 4679-4681, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2022.11.007.
Abstract: Chaperones are important for protein folding, but visualizing this process has proven to be exceptionally difficult. In this issue of Cell, Frydman and colleagues have succeeded in watching tubulin being folded by its chaperonin TRiC at near-atomic resolution.
Daniel Gestaut, Yanyan Zhao, Junsun Park, Boxue Ma, Alexander Leitner, Miranda Collier, Grigore Pintilie, Soung-Hun Roh, Wah Chiu, Judith Frydman
Cell, Volume 185, Issue 25,2022, Pages 4770-4787.e20,ISSN 0092-8674 https://doi.org/10.1016/j.cell.2022.11.014. (https://www.sciencedirect.com/science/article/pii/S009286742201457X)