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Title | Structural underpinnings of Ric8A function as a G-protein α-subunit chaperone and guanine-nucleotide exchange factor. |
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Journal, issue, pages | Nat Commun, Vol. 10, Issue 1, Page 3084, Year 2019 |
Publish date | Jul 12, 2019 |
Authors | Dhiraj Srivastava / Lokesh Gakhar / Nikolai O Artemyev / |
PubMed Abstract | Resistance to inhibitors of cholinesterase 8A (Ric8A) is an essential regulator of G protein α-subunits (Gα), acting as a guanine nucleotide exchange factor and a chaperone. We report two crystal ...Resistance to inhibitors of cholinesterase 8A (Ric8A) is an essential regulator of G protein α-subunits (Gα), acting as a guanine nucleotide exchange factor and a chaperone. We report two crystal structures of Ric8A, one in the apo form and the other in complex with a tagged C-terminal fragment of Gα. These structures reveal two principal domains of Ric8A: an armadillo-fold core and a flexible C-terminal tail. Additionally, they show that the Gα C-terminus binds to a highly-conserved patch on the concave surface of the Ric8A armadillo-domain, with selectivity determinants residing in the Gα sequence. Biochemical analysis shows that the Ric8A C-terminal tail is critical for its stability and function. A model of the Ric8A/Gα complex derived from crosslinking mass spectrometry and molecular dynamics simulations suggests that the Ric8A C-terminal tail helps organize the GTP-binding site of Gα. This study lays the groundwork for understanding Ric8A function at the molecular level. |
External links | Nat Commun / PubMed:31300652 / PubMed Central |
Methods | SAS (X-ray synchrotron) / X-ray diffraction |
Resolution | 1.75 - 3.9 Å |
Structure data | SASDF65: SASDF75: PDB-6n84: PDB-6n85: PDB-6n86: |
Chemicals | ChemComp-SO4: ChemComp-HOH: |
Source |
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Keywords | CHAPERONE / G alpha / MBP / Ric8a / Armadillo repeat |