| First Author | Papasergi-Scott MM | Year | 2023 |
| Journal | Structure | Volume | 31 |
| Issue | 5 | Pages | 553-564.e7 |
| PubMed ID | 36931277 | Mgi Jnum | J:352586 |
| Mgi Id | MGI:7707641 | Doi | 10.1016/j.str.2023.02.011 |
| Citation | Papasergi-Scott MM, et al. (2023) Structures of Ric-8B in complex with Galpha protein folding clients reveal isoform specificity mechanisms. Structure 31(5):553-564.e7 |
| abstractText | Mammalian Ric-8 proteins act as chaperones to regulate the cellular abundance of heterotrimeric G protein alpha subunits. The Ric-8A isoform chaperones Galphai/o, Galpha12/13, and Galphaq/11 subunits, while Ric-8B acts on Galphas/olf subunits. Here, we determined cryoelectron microscopy (cryo-EM) structures of Ric-8B in complex with Galphas and Galphaolf, revealing isoform differences in the relative positioning and contacts between the C-terminal alpha5 helix of Galpha within the concave pocket formed by Ric-8 alpha-helical repeat elements. Despite the overall architectural similarity with our earlier structures of Ric-8A complexed to Galphaq and Galphai1, Ric-8B distinctly accommodates an extended loop found only in Galphas/olf proteins. The structures, along with results from Ric-8 protein thermal stability assays and cell-based Galphaolf folding assays, support a requirement for the Galpha C-terminal region for binding specificity, and highlight that multiple structural elements impart specificity for Ric-8/G protein binding. |
