It takes two to tango: regulation of G proteins by dimerization.
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.
Gasper
Raphael
R
Max-Planck-Institut für Molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany.
Meyer
Simon
S
Gotthardt
Katja
K
Sirajuddin
Minhajuddin
M
Wittinghofer
Alfred
A
D017607:Aluminum Compounds / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D005459:Fluorides / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary
D017607:Aluminum Compounds; D010940:Plant Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D005459:Fluorides; C032311:aluminum fluoride