In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 16, No. 772 ( 2023-02-14)
Abstract:
Ligand binding to a GPCR leads to G protein activation through the displacement of GDP by GTP at the α-subunit and the subsequent dissociation of Gα from Gβγ. The GTPase activity of Gα, which depends on a conserved glutamine residue, hydrolyzes GTP to GDP, thereby deactivating the G protein. Noting that rare mutations of the catalytic glutamine residue confer constitutive activity to some G proteins, Hewitt et al . analyzed the effect of mutating this residue to all other possible residues in multiple G protein α-subunits. Through biochemical, functional, and structural studies, the authors showed that whereas all possible mutants tested exhibited no GTPase activity, not all were constitutively active, some retained the ability to be further activated or inhibited by GPCRs, and some still bound to Gβγ. In addition, different mutations resulted in the generation of multiple active state conformations. These data suggest that the role of this conserved glutamine residue goes beyond catalysis to regulate G protein structure and function. —JFF
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.abq7842
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023
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