title: The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation.
abstract: In animals, heterotrimeric guanine nucleotide-binding protein (G protein) signaling is initiated by G protein-coupled receptors (GPCRs), which activate G protein α subunits; however, the plant Arabidopsis thaliana lacks canonical GPCRs, and its G protein α subunit (AtGPA1) is self-activating. To investigate how AtGPA1 becomes activated, we determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage from the Ras domain of the protein. Domain substitution experiments showed that the helical domain of AtGPA1 was necessary for self-activation and sufficient to confer self-activation to an animal G protein α subunit. These findings reveal the structural basis for a mechanism for G protein activation in Arabidopsis that is distinct from the well-established mechanism found in animals.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Janice C
authors.initials: JC
authors.lastname: Jones
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Duffy
authors.forename: Mischa
authors.initials: M
authors.lastname: Machius
authors.forename: Brenda R S
authors.initials: BR
authors.lastname: Temple
authors.forename: Henrik G
authors.initials: HG
authors.lastname: Dohlman
authors.forename: Alan M
authors.initials: AM
authors.lastname: Jones
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002942:Circular Dichroism; D003460:Crystallization; D044385:GTP-Binding Protein alpha Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014961:X-Ray Diffraction
chemical_list: D029681:Arabidopsis Proteins; C429765:GPA1 protein, Arabidopsis; D044385:GTP-Binding Protein alpha Subunits; D020662:Guanine Nucleotide Exchange Factors; D043562:Receptors, G-Protein-Coupled; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate