Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi-native conformations.
Three-dimensional reconstruction from cryoelectron micrographs of the eukaryotic cytosolic chaperonin CCT complexed to tubulin shows that CCT interacts with tubulin (both the alpha and beta isoforms) using five specific CCT subunits. The CCT-tubulin interaction has a different geometry to the CCT-actin interaction, and a mixture of shared and unique CCT subunits is used in binding the two substrates. Docking of the atomic structures of both actin and tubulin to their CCT-bound conformation suggests a common mode of chaperonin-substrate interaction. CCT stabilizes quasi-native structures in both proteins that are open through their domain-connecting hinge regions, suggesting a novel mechanism and function of CCT in assisted protein folding.
Llorca
O
O
Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Martín-Benito
J
J
Ritco-Vonsovici
M
M
Grantham
J
J
Hynes
G M
GM
Willison
K R
KR
Carrascosa
J L
JL
Valpuesta
J M
JM
D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D001665:Binding Sites; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D004355:Drug Stability; D019143:Evolution, Molecular; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D014404:Tubulin / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*
D000199:Actins; D001059:Apoproteins; D021122:Protein Subunits; D011994:Recombinant Proteins; D014404:Tubulin; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins