6TYL

Crystal structure of mammalian Ric-8A:Galpha(i):nanobody complex

Summary for 6TYL

• Entry DOI: 10.2210/pdb6tyl/pdb
• Descriptor: Resistance to inhibitors of cholinesterase 8 homolog A (C. elegans), Nanobody A, Nanobody B, ... (5 entities in total)
• Functional Keywords: ric-8a, g protein, gef, signaling protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 10
• Total formula weight: 277975.80

Authors

Mou, T.C.,McClelland, L.,Yates-Hansen, C.,Sprang, S.R. (deposition date: 2019-08-09, release date: 2020-03-11, Last modification date: 2024-11-20)

Primary citation

McClelland, L.J.,Zhang, K.,Mou, T.C.,Johnston, J.,Yates-Hansen, C.,Li, S.,Thomas, C.J.,Doukov, T.I.,Triest, S.,Wohlkonig, A.,Tall, G.G.,Steyaert, J.,Chiu, W.,Sprang, S.R.
Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to G alpha i1.
Nat Commun, 11:1077-1077, 2020

PubMed Abstract: Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) and serves as an essential Gα chaperone. Mechanisms by which Ric-8A catalyzes these activities, which are stimulated by Casein Kinase II phosphorylation, are unknown. We report the structure of the nanobody-stabilized complex of nucleotide-free Gα bound to phosphorylated Ric-8A at near atomic resolution by cryo-electron microscopy and X-ray crystallography. The mechanism of Ric-8A GEF activity differs considerably from that employed by G protein-coupled receptors at the plasma membrane. Ric-8A engages a specific conformation of Gα at multiple interfaces to form a complex that is stabilized by phosphorylation within a Ric-8A segment that connects two Gα binding sites. The C-terminus of Gα is ejected from its beta sheet core, thereby dismantling the GDP binding site. Ric-8A binds to the exposed Gα beta sheet and switch II to stabilize the nucleotide-free state of Gα.

PubMed: 32103024
DOI: 10.1038/s41467-020-14943-4

Experimental method

X-RAY DIFFRACTION (3.3 Å)