Figure 2
From: CCT2 Mutations Evoke Leber Congenital Amaurosis due to Chaperone Complex Instability
Molecular modeling for CCTβ and two CCTβ Mutant Variants.
Molecular modeling of atomic structures for the CCTβ subunit, its variants and the corresponding CCT ring complexes. Structures of the variants, T400P and R516H, are presented in Panels A–C and D–F, respectively. (A) Predicted structures for the CCT hetero-octamer, the T400P mutant CCTβ subunit and the proline residue at position 400 are shown in light grey, blue and yellow, respectively. (B) Structures of wild-type CCTβ (light grey) and the T400P mutant variant (light blue) are superimposed. (C) The T400P mutant protein structure reveals a break in the α-helix (residues 380–401) at the C-terminus. (D) Mutation R516H (red) is located in the inter-subunit interface of the CCT protein structure (grey). The structure for the R516H CCTβ mutant subunit is shown in blue. The histidine residue at position 516 is shown in red. (E) Structures of wild-type CCTβ (light grey) and the R516H mutant variant (light blue) are superimposed. (F) Mutation R516H at the surface of the subunit is predicted to decrease the stability of α-helix 18. An ADP molecule bound to the CCTβ subunit is green. Hydrogen bonds are blue. (G) Top view of the CCT hetero-octamer. (H) Oligomerization of wild-type CCTβ with the other CCT subunits is shown (Upper: top view, Lower: side view). (I) Oligomerization of the T400P variant with the other CCT subunits is shown (Upper: top view, Lower: side view). The α-helix of the T400P variant exhibited closer orientation to CCTγ than that of wild-type CCTβ as indicated with a white arrow. (J) Oligomerization of the R516H variant with the other CCT subunits is shown (Upper: top view, Lower: side view). The R516H variant and CCTγ are more separated than wild type CCTβ and CCTγ (indicated with a white arrow head). The T400P and R516H mutants are predicted to affect the intra-ring structure of the CCT complex.
