Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis

Cell. 1997 Apr 18;89(2):251-61. doi: 10.1016/s0092-8674(00)80204-4.


RGS proteins are GTPase activators for heterotrimeric G proteins. We report here the 2.8 A resolution crystal structure of the RGS protein RGS4 complexed with G(i alpha1)-Mg2+-GDP-AlF4 . Only the core domain of RGS4 is visible in the crystal. The core domain binds to the three switch regions of G(i alpha1), but does not contribute catalytic residues that directly interact with either GDP or AlF4-. Therefore, RGS4 appears to catalyze rapid hydrolysis of GTP primarily by stabilizing the switch regions of G(i alpha1), although the conserved Asn-128 from RGS4 could also play a catalytic role by interacting with the hydrolytic water molecule or the side chain of Gln-204. The binding site for RGS4 on G(i alpha1) is also consistent with the activity of RGS proteins as antagonists of G(alpha) effectors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aluminum Compounds / chemistry
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Fluorides / chemistry
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / chemistry*
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Guanosine Diphosphate / chemistry
  • Guanosine Triphosphate / metabolism*
  • Hydrolysis
  • Magnesium / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation*
  • Proteins / chemistry*
  • Proteins / metabolism
  • RGS Proteins*
  • Rats


  • Aluminum Compounds
  • Proteins
  • RGS Proteins
  • Guanosine Diphosphate
  • RGS4 protein
  • tetrafluoroaluminate
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Magnesium
  • Fluorides