Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A

Cell. 1999 Feb 5;96(3):363-74. doi: 10.1016/s0092-8674(00)80549-8.

Abstract

The small G protein Rab3A plays an important role in the regulation of neurotransmitter release. The crystal structure of activated Rab3A/GTP/Mg2+ bound to the effector domain of rabphilin-3A was solved to 2.6 A resolution. Rabphilin-3A contacts Rab3A in two distinct areas. The first interface involves the Rab3A switch I and switch II regions, which are sensitive to the nucleotide-binding state of Rab3A. The second interface consists of a deep pocket in Rab3A that interacts with a SGAWFF structural element of rabphilin-3A. Sequence and structure analysis, and biochemical data suggest that this pocket, or Rab complementarity-determining region (RabCDR), establishes a specific interaction between each Rab protein and its effectors. RabCDRs could be major determinants of effector specificity during vesicle trafficking and fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cattle
  • Crystallization
  • Crystallography, X-Ray
  • Dimerization
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / isolation & purification
  • Humans
  • Macromolecular Substances
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / isolation & purification
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / isolation & purification
  • Rats
  • Vesicular Transport Proteins
  • rab GTP-Binding Proteins*
  • rab3 GTP-Binding Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Macromolecular Substances
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Vesicular Transport Proteins
  • rabphilin-3A
  • GTP-Binding Proteins
  • rab GTP-Binding Proteins
  • rab3 GTP-Binding Proteins

Associated data

  • PDB/1ZBD