8I6J

The focused refinement of CCT3-PhLP2A from TRiC-PhLP2A complex in the open state

Summary for 8I6J

• Entry DOI: 10.2210/pdb8i6j/pdb
• Related: 8I1U 8I9Q 8I9U 8IB8
• EMDB information: 35122 35199 35280 35284 35335
• Descriptor: Phosducin-like protein 3, T-complex protein 1 subunit gamma, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: chaperonin complex, chaperone, cochaperone
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 88691.44

Authors

Roh, S.H.,Park, J.,Kim, H.,Lim, S. (deposition date: 2023-01-28, release date: 2024-01-31, Last modification date: 2024-05-08)

Primary citation

Park, J.,Kim, H.,Gestaut, D.,Lim, S.,Opoku-Nsiah, K.A.,Leitner, A.,Frydman, J.,Roh, S.H.
A structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle.
Nat Commun, 15:1007-1007, 2024

PubMed Abstract: Proper cellular proteostasis, essential for viability, requires a network of chaperones and cochaperones. ATP-dependent chaperonin TRiC/CCT partners with cochaperones prefoldin (PFD) and phosducin-like proteins (PhLPs) to facilitate folding of essential eukaryotic proteins. Using cryoEM and biochemical analyses, we determine the ATP-driven cycle of TRiC-PFD-PhLP2A interaction. PhLP2A binds to open apo-TRiC through polyvalent domain-specific contacts with its chamber's equatorial and apical regions. PhLP2A N-terminal H3-domain binding to subunits CCT3/4 apical domains displace PFD from TRiC. ATP-induced TRiC closure rearranges the contacts of PhLP2A domains within the closed chamber. In the presence of substrate, actin and PhLP2A segregate into opposing chambers, each binding to positively charged inner surface residues from CCT1/3/6/8. Notably, actin induces a conformational change in PhLP2A, causing its N-terminal helices to extend across the inter-ring interface to directly contact a hydrophobic groove in actin. Our findings reveal an ATP-driven PhLP2A structural rearrangement cycle within the TRiC chamber to facilitate folding.

PubMed: 38307855
DOI: 10.1038/s41467-024-45242-x

Experimental method

ELECTRON MICROSCOPY (3.82 Å)