6NMG

Crystal Structure of Rat Ric-8A G alpha binding domain

Summary for 6NMG

• Entry DOI: 10.2210/pdb6nmg/pdb
• Descriptor: Resistance to inhibitors of cholinesterase 8 homolog A (C. elegans), SULFATE ION (3 entities in total)
• Functional Keywords: guanine nucleotide exchange factor heterotrimeric g protein alpha subunit g alpha i(1), signaling protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 2
• Total formula weight: 102703.89

Authors

Zeng, B.,Mou, T.C.,Sprang, S.R. (deposition date: 2019-01-10, release date: 2019-06-26, Last modification date: 2024-03-13)

Primary citation

Zeng, B.,Mou, T.C.,Doukov, T.I.,Steiner, A.,Yu, W.,Papasergi-Scott, M.,Tall, G.G.,Hagn, F.,Sprang, S.R.
Structure, Function, and Dynamics of the G alpha Binding Domain of Ric-8A.
Structure, 27:1137-1147.e5, 2019

PubMed Abstract: 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 (Gα). We report the 2.2-Å crystal structure of the Ric-8A Gα-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 Gα-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 H-N-TROSY spectra of [H,N]-labeled Gαi1 in the presence of R452 reveals chemical shift perturbations of the C terminus and Gαi1 residues involved in nucleotide binding.

PubMed: 31155309
DOI: 10.1016/j.str.2019.04.013

Experimental method

X-RAY DIFFRACTION (2.2 Å)