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8el8

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

Structural highlights

8el8 is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GNAL_HUMAN Autosomal dominant focal dystonia, DYT25 type. The disease is caused by variants affecting the gene represented in this entry.

Function

GNAL_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(olf) alpha mediates signal transduction within the olfactory neuroepithelium and the basal ganglia. May be involved in some aspect of visual transduction, and in mediating the effect of one or more hormones/neurotransmitters.

Publication Abstract from PubMed

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.

Structures of Ric-8B in complex with Galpha protein folding clients reveal isoform specificity mechanisms.,Papasergi-Scott MM, Kwarcinski FE, Yu M, Panova O, Ovrutsky AM, Skiniotis G, Tall GG Structure. 2023 May 4;31(5):553-564.e7. doi: 10.1016/j.str.2023.02.011. Epub 2023 , Mar 16. PMID:36931277^[1]

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

References

↑ Papasergi-Scott MM, Kwarcinski FE, Yu M, Panova O, Ovrutsky AM, Skiniotis G, Tall GG. Structures of Ric-8B in complex with Gα protein folding clients reveal isoform specificity mechanisms. Structure. 2023 May 4;31(5):553-564.e7. PMID:36931277 doi:10.1016/j.str.2023.02.011