It takes two to tango: regulation of G proteins by dimerization

Nat Rev Mol Cell Biol. 2009 Jun;10(6):423-9. doi: 10.1038/nrm2689. Epub 2009 May 8.

Abstract

Guanine nucleotide-binding (G) proteins, which cycle between a GDP- and a GTP-bound conformation, are conventionally regulated by GTPase-activating proteins (GAPs) and guanine nucleotide-exchange factors (GEFs), and function by interacting with effector proteins in the GTP-bound 'on' state. Here we present another class of G proteins that are regulated by homodimerization, which we would categorize as G proteins activated by nucleotide-dependent dimerization (GADs). This class includes proteins such as signal recognition particle (SRP), dynamin, septins and the newly discovered Roco protein Leu-rich repeat kinase 2 (LRRK2). We propose that the juxtaposition of the G domains of two monomers across the GTP-binding sites activates the biological function of these proteins and the GTPase reaction.

Publication types

  • Review

MeSH terms

  • Aluminum Compounds / metabolism
  • Animals
  • Binding Sites
  • Dimerization
  • Fluorides / metabolism
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Models, Molecular
  • Plant Proteins / chemistry
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Protein Structure, Quaternary*

Substances

  • Aluminum Compounds
  • Plant Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Fluorides
  • aluminum fluoride

Associated data

  • PDB/2B92
  • PDB/2BC9
  • PDB/2CNW
  • PDB/2GJ8
  • PDB/2HF8