Fig. 1: Structure and sequence comparisons of subunit CCT2 in CCT/TRiC from different organisms.

a Crystal structure of yeast subunit CCT2 (PDB ID: 4V8R) in the ADP-bound state showing the mutated residues (red), helices 14 (cyan) and 18 (gold), and ADP (green). The contact site between helix 14 and ADP is magnified. It can be seen that a mutation at position 394 can have an allosteric effect on E489, which is in contact with ADP, via S490. A mutation at position 510 can affect ADP via a rigid-body movement of helix 18. Also shown is D386 (pink), which is a conserved catalytic residue. b Alignment of the sequences of helix 14 (top) and helix 18 and strand 25 (bottom) in subunit CCT2 from different organisms. The mutated positions are highlighted in cyan and other conserved positions in yellow. The numbering corresponds to yeast CCT2. The overall amino acid sequence identities of yeast and human helix 14, helix 18 and strand 25 and the entire CCT2 subunit are about 78, 71, and 65%, respectively. The corresponding sequence similarities are about 87, 92 and 80%, respectively. c Superimposed cryo-EM structure of human CCT2 (PDB ID: 7LUM) and the crystal structure of yeast CCT2 (PDB ID: 4V8R) both in the closed state. The structures are very similar as indicated by a root mean square deviation of ~1.2 Å. Panels a and c were generated using Chimera version 1.15. The single-letter code of amino acids is used.