التفاصيل البيبلوغرافية
| العنوان: |
Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1. |
| المؤلفون: |
McClelland, Levi J., Zhang, Kaiming, Mou, Tung-Chung, Johnston, Jake, Yates-Hansen, Cindee, Li, Shanshan, Thomas, Celestine J., Doukov, Tzanko I., Triest, Sarah, Wohlkonig, Alexandre, Tall, Gregory G., Steyaert, Jan, Chiu, Wah, Sprang, Stephen R. |
| المصدر: |
Nature Communications; 2/26/2020, Vol. 11 Issue 1, p1-10, 10p |
| مصطلحات موضوعية: |
GUANINE nucleotide exchange factors, MOLECULAR chaperones, G proteins, PROTEIN kinase CK2, PROTEIN structure, G protein coupled receptors |
| مستخلص: |
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. Ric-8A is guanine nucleotide exchange factor (GEF) that also acts as a folding chaperone for its Gα subunit. Here, the authors present the structure of Ric-8A bound to nucleotide-free Gαi1, revealing the mechanism by which Ric-8A exerts both GEF and chaperone activity. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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