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Publication Abstract from PubMed

Ric-8A is a 530-amino acid cytoplasmic molecular chaperone and guanine nucleotide exchange factor (GEF) for i, q, and 12/13 classes of heterortrimeric G protein alpha subunits (Galpha). We report the 2.2-A crystal structure of the Ric-8A Galpha-binding domain with GEF activity, residues 1-452, and is phosphorylated at Ser435 and Thr440. Residues 1-429 adopt a superhelical fold comprised of Armadillo (ARM) and HEAT repeats, and the C terminus is disordered. One of the phosphorylated residues potentially binds to a basic cluster in an ARM motif. Amino acid sequence conservation and published hydrogen-deuterium exchange data indicate repeats 3 through 6 to be a putative Galpha-binding surface. Normal mode modeling of small-angle X-ray scattering data indicates that phosphorylation induces relative rotation between repeats 1-4, 5-6, and 7-9. 2D (1)H-(15)N-TROSY spectra of [(2)H,(15)N]-labeled Galphai1 in the presence of R452 reveals chemical shift perturbations of the C terminus and Galphai1 residues involved in nucleotide binding.

Structure, Function, and Dynamics of the Galpha Binding Domain of Ric-8A.,Zeng B, Mou TC, Doukov TI, Steiner A, Yu W, Papasergi-Scott M, Tall GG, Hagn F, Sprang SR Structure. 2019 Jul 2;27(7):1137-1147.e5. doi: 10.1016/j.str.2019.04.013. Epub, 2019 May 30. PMID:31155309^[1]

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