Structures of Gα Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms
Alpay B. Seven, Daniel Hilger, Makaía M. Papasergi-Scott, Li Zhang, Qianhui Qu, Brian K. Kobilka, Gregory G. Tall, Georgios Skiniotis
Abstract
complexes reveal that the chaperone employs its extended C-terminal region to cradle the Ras-like domain of Gα, positioning the Ras core in contact with the Ric-8A core while engaging its switch2 nucleotide binding region. The C-terminal α5 helix of Gα is held away from the Ras-like domain through Ric-8A core domain interactions, which critically depend on recognition of the Gα C terminus by the chaperone. The structures, complemented with biochemical and cellular chaperoning data, support a folding quality control mechanism that ensures proper formation of the C-terminal α5 helix before allowing GTP-gated release of Gα from Ric-8A.