Research ArticleG Proteins

The Crystal Structure of a Self-Activating G Protein α Subunit Reveals Its Distinct Mechanism of Signal Initiation

Science Signaling  08 Feb 2011:
Vol. 4, Issue 159, pp. ra8
DOI: 10.1126/scisignal.2001446

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Helical Movement

Signaling by heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) in animals is a well-studied process. Binding of ligand to the GPCR results in a conformational change that activates the G protein by inducing the exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) at the G protein α subunit. The resulting dissociation of the heterotrimer frees the α and βγ subunits to interact with effector molecules. Arabidopsis lacks the canonical GPCRs of animal cells, and its G protein α subunit, AtGPA1, is self-activating, exhibiting spontaneous nucleotide exchange. Jones et al. solved the crystal structure of AtGPA1 and compared it to that of a mammalian Gαi1. This analysis showed that the helical domain region of AtGPA1 was disordered compared to that of Gαi1, and molecular dynamics simulations demonstrated its dynamic motion. Substitution of the Gαi1 helical domain with that of AtGPA1 made the resulting chimeric protein self-activating, demonstrating that the helical domain of AtGPA1 regulates nucleotide exchange and endows the plant α subunit with a distinct mechanism of activation.

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