Journal article
Ric‐8A, a GEF, and a Chaperone for G Protein α‐Subunits: Evidence for the Two‐Faced Interface
BioEssays, Vol.42(3), pp.1900208-n/a
03/2020
DOI: 10.1002/bies.201900208
PMID: 31967346
Abstract
Resistance to inhibitors of cholinesterase 8A (Ric‐8A) is a prominent non‐receptor GEF and a chaperone of G protein α‐subunits (Gα). Recent studies shed light on the structure of Ric‐8A, providing insights into the mechanisms underlying its interaction with Gα. Ric‐8A is composed of a core armadillo‐like domain and a flexible C‐terminal tail. Interaction of a conserved concave surface of its core domain with the Gα C‐terminus appears to mediate formation of the initial Ric‐8A/GαGDP intermediate, followed by the formation of a stable nucleotide‐free complex. The latter event involves a large‐scale dislocation of the Gα α5‐helix that produces an extensive primary interface and disrupts the nucleotide‐binding site of Gα. The distal portion of the C‐terminal tail of Ric‐8A forms a smaller secondary interface, which ostensibly binds the switch II region of Gα, facilitating binding of GTP. The two‐site Gα interface of Ric‐8A is distinct from that of GPCRs, and might have evolved to support the chaperone function of Ric‐8A.
Details
- Title: Subtitle
- Ric‐8A, a GEF, and a Chaperone for G Protein α‐Subunits: Evidence for the Two‐Faced Interface
- Creators
- Dhiraj Srivastava - Department of Molecular Physiology and BiophysicsThe University of Iowa Carver College of Medicine Iowa City IA 52242 USANikolai O Artemyev - Department of Molecular Physiology and BiophysicsThe University of Iowa Carver College of Medicine Iowa City IA 52242 USA, Department of Ophthalmology and Visual SciencesThe University of Iowa Carver College of Medicine Iowa City IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- BioEssays, Vol.42(3), pp.1900208-n/a
- DOI
- 10.1002/bies.201900208
- PMID
- 31967346
- NLM abbreviation
- Bioessays
- ISSN
- 0265-9247
- eISSN
- 1521-1878
- Grant note
- name: NIH National Eye Institute, award: RO1 EY-12682
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070121002771
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