Role of the 14-3-3 C-terminal loop in ligand interaction.
14-3-3 proteins are a family of conserved dimeric molecules that interact with a broad range of target proteins, most of which contain phosphoserine/threonine. The amphipathic groove of 14-3-3 is the main structural feature involved in mediating its associations. We have studied another domain of 14-3-3, the C-terminal loop, to determine what role it plays in ligand interaction. A truncated form of 14-3-3zeta lacking this C-terminal loop was generated and found to bind with higher affinity than the wild-type 14-3-3zeta protein to the ligands Raf-1 and Bad. Interestingly, the truncated 14-3-3zeta also showed increased association with the 14-3-3 binding-deficient Bad/S136A mutant. Taken together, these data support a role for the C-terminal loop as a general inhibitor of 14-3-3/ligand interactions. This may provide a mechanism by which inappropriate associations with 14-3-3 are prevented.
D048948:14-3-3 Proteins; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D017384:Sequence Deletion; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051025:bcl-Associated Death Protein
D048948:14-3-3 Proteins; C494819:BAD protein, human; D002352:Carrier Proteins; D008024:Ligands; D051025:bcl-Associated Death Protein; D014446:Tyrosine 3-Monooxygenase; D019908:Proto-Oncogene Proteins c-raf