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Ric‐8A, a GEF, and a Chaperone for G Protein α‐Subunits: Evidence for the Two‐Faced Interface
Journal article   Peer reviewed

Ric‐8A, a GEF, and a Chaperone for G Protein α‐Subunits: Evidence for the Two‐Faced Interface

Dhiraj Srivastava and Nikolai O Artemyev
BioEssays, Vol.42(3), pp.1900208-n/a
03/2020
DOI: 10.1002/bies.201900208
PMID: 31967346
url
https://www.ncbi.nlm.nih.gov/pmc/articles/7034654View
Open Access

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.

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