Structural highlights
FunctionPFD1_HUMAN Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. Publication Abstract from PubMedThe 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 beta-tubulin using human prefoldin and TRiC. We find unstructured beta-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 beta-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. 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. 2022 Dec 8;185(25):4770-4787.e20. doi: 10.1016/j.cell.2022.11.014. PMID:36493755[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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