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- SASDF65: Resistance to inhibitors of cholinesterase 8 homolog A (Ric8a) am... -

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Basic information

Entry
Database: SASBDB / ID: SASDF65
SampleResistance to inhibitors of cholinesterase 8 homolog A (Ric8a) amino acids 1-492
  • Resistance to inhibitors of cholinesterase 8 homolog A (protein), Ric8a, Bos taurus
Function / homology
Function and homology information


G-protein alpha-subunit binding / guanyl-nucleotide exchange factor activity / G protein-coupled receptor signaling pathway / plasma membrane / cytoplasm
Similarity search - Function
Synembryn / Guanine nucleotide exchange factor, Ric8 / Guanine nucleotide exchange factor synembryn / Armadillo-like helical / Armadillo-type fold
Similarity search - Domain/homology
Biological speciesBos taurus (cattle)
CitationJournal: Nat Commun / Year: 2019
Title: Structural underpinnings of Ric8A function as a G-protein α-subunit chaperone and guanine-nucleotide exchange factor.
Authors: Dhiraj Srivastava / Lokesh Gakhar / Nikolai O Artemyev /
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.
Contact author
  • Dhiraj Srivastava (University of Iowa, Iowa, USA)

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Models

Model #3128
Type: atomic / Comment: One state model / Chi-square value: 1.50747614912
Search similar-shape structures of this assembly by Omokage search (details)
Model #3129
Type: atomic / Comment: Fractional contribution in X-ray scattering: 59% / Chi-square value: 1.19852188057
Search similar-shape structures of this assembly by Omokage search (details)
Model #3130
Type: atomic / Comment: Fractional contribution in X-ray scattering: 29% / Chi-square value: 1.19852188057
Search similar-shape structures of this assembly by Omokage search (details)
Model #3131
Type: atomic / Comment: Fractional contribution in X-ray scattering: 12% / Chi-square value: 1.19852188057
Search similar-shape structures of this assembly by Omokage search (details)

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Sample

SampleName: Resistance to inhibitors of cholinesterase 8 homolog A (Ric8a) amino acids 1-492
Specimen concentration: 10 mg/ml
BufferName: 20 mM Tris, 150 mM KCl, 5 % glycerol, 1 mM TCEP / pH: 8
Entity #1575Name: Ric8a / Type: protein
Description: Resistance to inhibitors of cholinesterase 8 homolog A
Formula weight: 55.643 / Num. of mol.: 1 / Source: Bos taurus / References: UniProt: Q5E9J8
Sequence: GHMADPRAVA DALETGEEDV VMEALRAYNR ENSQSFTFDD AQQEDRKRLA KLLVSVLEQG LPPSRRVIWL QSIRILSRDR SCLDSFTSRR SLQALACYAG ISASQGSVPE PLNMDVVLES LKCLCNLVLS SPVAQALAAE AGLVVRLAER VGLCRQSSFP HDVQFFDLRL ...Sequence:
GHMADPRAVA DALETGEEDV VMEALRAYNR ENSQSFTFDD AQQEDRKRLA KLLVSVLEQG LPPSRRVIWL QSIRILSRDR SCLDSFTSRR SLQALACYAG ISASQGSVPE PLNMDVVLES LKCLCNLVLS SPVAQALAAE AGLVVRLAER VGLCRQSSFP HDVQFFDLRL LFLLTALRTD VRQQLFQELQ GVRLLTRALE LTLGMTEGER HPELLPPQET ERAMEILKVL FNITFDSIKR EVDEEDAALY RHLGTLLRHC VMLAAAGDRT EELHGHAVNL LGNLPVKCLD VLLTLEPHEG SLEFLGVNMD VIRVLLSFME KRLHQTHRLK ESVAPVLSVL TECARMHRPA RKFLKAQVLP PLRDVRTRPE VGELLRNKLV RLMTHLDTDV KRVAAEFLFV LCSESVPRFI KYTGYGNAAG LLAARGLMAG GRPEGQYSED EDTDTDEYKE AKASINPVTG RVEEKPPNPM EGMTEEQKEH EAMKLVNMFD KLSRH

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Experimental information

BeamInstrument name: Advanced Photon Source (APS), Argonne National Laboratory BioCAT 18ID
City: Lemont, IL / : USA / Type of source: X-ray synchrotron / Wavelength: 0.1033 Å / Dist. spec. to detc.: 3.5 mm
DetectorName: Pilatus3 X 1M / Pixsize x: 0.172 mm
Scan
Title: Resistance to inhibitors of cholinesterase 8 homolog A (Ric8a) amino acids 1-492
Measurement date: Oct 27, 2018 / Storage temperature: 4 °C / Cell temperature: 25 °C / Exposure time: 0.5 sec. / Unit: 1/A /
MinMax
Q0.0054 0.3813
Distance distribution function P(R)
Sofotware P(R): GNOM 5.0 / Number of points: 750 /
MinMax
Q0.0126276 0.237683
P(R) point1 750
R0 127
Result
Type of curve: sec /
ExperimentalPorod
MW64.6 kDa55 kDa
Volume-88 nm3

P(R)GuinierGuinier error
Forward scattering, I00.002138 0.00212099 2.0E-6
Radius of gyration, Rg3.5 nm3.37 nm0.1

MinMax
D-12.7
Guinier point25 111

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