The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation

Sci Signal. 2011 Feb 8;4(159):ra8. doi: 10.1126/scisignal.2001446.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism
  • Circular Dichroism
  • Crystallization
  • GTP-Binding Protein alpha Subunits / chemistry*
  • GTP-Binding Protein alpha Subunits / genetics
  • GTP-Binding Protein alpha Subunits / metabolism
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / metabolism
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein Folding
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • X-Ray Diffraction

Substances

  • Arabidopsis Proteins
  • GPA1 protein, Arabidopsis
  • GTP-Binding Protein alpha Subunits
  • Guanine Nucleotide Exchange Factors
  • Receptors, G-Protein-Coupled
  • Adenosine Diphosphate
  • Adenosine Triphosphate