8EL8

CryoEM structure of Resistance to Inhibitors of Cholinesterase-8B (Ric-8B) in complex with olfactory G protein alpha olf

Summary for 8EL8

• Entry DOI: 10.2210/pdb8el8/pdb
• EMDB information: 28224
• Descriptor: Guanine nucleotide-binding protein G(olf) subunit alpha, Isoform 1 of Synembryn-B (2 entities in total)
• Functional Keywords: chaperone, armadillo repeat, gef, ras, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 108298.47

Authors

Papasergi-Scott, M.M.,Skiniotis, G. (deposition date: 2022-09-23, release date: 2023-03-01, Last modification date: 2024-10-09)

Primary citation

Papasergi-Scott, M.M.,Kwarcinski, F.E.,Yu, M.,Panova, O.,Ovrutsky, A.M.,Skiniotis, G.,Tall, G.G.
Structures of Ric-8B in complex with G alpha protein folding clients reveal isoform specificity mechanisms.
Structure, 31:553-564.e7, 2023

PubMed Abstract: Mammalian Ric-8 proteins act as chaperones to regulate the cellular abundance of heterotrimeric G protein α subunits. The Ric-8A isoform chaperones Gαi/o, Gα12/13, and Gαq/11 subunits, while Ric-8B acts on Gαs/olf subunits. Here, we determined cryoelectron microscopy (cryo-EM) structures of Ric-8B in complex with Gαs and Gαolf, revealing isoform differences in the relative positioning and contacts between the C-terminal α5 helix of Gα within the concave pocket formed by Ric-8 α-helical repeat elements. Despite the overall architectural similarity with our earlier structures of Ric-8A complexed to Gαq and Gαi1, Ric-8B distinctly accommodates an extended loop found only in Gαs/olf proteins. The structures, along with results from Ric-8 protein thermal stability assays and cell-based Gαolf folding assays, support a requirement for the Gα C-terminal region for binding specificity, and highlight that multiple structural elements impart specificity for Ric-8/G protein binding.

PubMed: 36931277
DOI: 10.1016/j.str.2023.02.011

Experimental method

ELECTRON MICROSCOPY (3.2 Å)