Structures of G? Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.

ABSTRACT: Many chaperones promote nascent polypeptide folding followed by substrate release through ATP-dependent conformational changes. Here we show cryoEM structures of G? subunit folding intermediates in complex with full-length Ric-8A, a unique chaperone-client system in which substrate release is facilitated by guanine nucleotide binding to the client G protein. The structures of Ric-8A-G?i and Ric-8A-G?q complexes reveal that the chaperone employs its extended C-terminal region to cradle the Ras-like domain of G?, positioning the Ras core in contact with the Ric-8A core while engaging its switch2 nucleotide binding region. The C-terminal ?5 helix of G? is held away from the Ras-like domain through Ric-8A core domain interactions, which critically depend on recognition of the G? 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 ?5 helix before allowing GTP-gated release of G? from Ric-8A.

SUBMITTER: Seven AB 

PROVIDER: S-EPMC7192526 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature