Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Binding Sites, Cattle, Crystallization, Crystallography, X-Ray, Dimerization, GTP-Binding Proteins, Humans, Macromolecular Substances, Mice, Models, Molecular, Molecular Sequence Data, Nerve Tissue Proteins, Peptide Fragments, Protein Structure, Tertiary, Proto-Oncogene Proteins, Rats, Vesicular Transport Proteins, rab GTP-Binding Proteins, rab3 GTP-Binding Proteins
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Binding Sites, Cattle, Crystallization, Crystallography, X-Ray, Dimerization, GTP-Binding Proteins, Humans, Macromolecular Substances, Mice, Models, Molecular, Molecular Sequence Data, Nerve Tissue Proteins, Peptide Fragments, Protein Structure, Tertiary, Proto-Oncogene Proteins, Rats, Vesicular Transport Proteins, rab GTP-Binding Proteins, rab3 GTP-Binding Proteins
Cell
Date: Feb. 05, 1999
PubMed ID: 10025402
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