6vu5

Publication Abstract from PubMed

Many chaperones promote nascent polypeptide folding followed by substrate release through ATP-dependent conformational changes. Here we show cryoEM structures of Galpha 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-Galphai and Ric-8A-Galphaq complexes reveal that the chaperone employs its extended C-terminal region to cradle the Ras-like domain of Galpha, positioning the Ras core in contact with the Ric-8A core while engaging its switch2 nucleotide binding region. The C-terminal alpha5 helix of Galpha is held away from the Ras-like domain through Ric-8A core domain interactions, which critically depend on recognition of the Galpha 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 alpha5 helix before allowing GTP-gated release of Galpha from Ric-8A.

Structures of Galpha Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.,Seven AB, Hilger D, Papasergi-Scott MM, Zhang L, Qu Q, Kobilka BK, Tall GG, Skiniotis G Cell Rep. 2020 Feb 28. pii: S2211-1247(20)30260-6. doi:, 10.1016/j.celrep.2020.02.086. PMID:32126208^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.