July 12, 1996Science
Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP
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Discussion
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Implication
Structural analysis reveals rapamycin bridging FKBP12 and the FRB domain of human FRAP, highlighting how small molecules mediate protein dimerization.
Key Points
- To determine the structural basis of the ternary complex formed by rapamycin interacting simultaneously with FKBP12 and the FRB domain of human FRAP.
- Determined the X-ray crystal structure of the ternary complex containing human FKBP12, rapamycin, and the FRB domain of human FRAP at a resolution of 2.7 angstroms.
- Demonstrated that rapamycin bridges FKBP12 and FRAP by simultaneously occupying distinct hydrophobic binding pockets on each protein, featuring extensive drug-protein contacts but minimal direct protein-protein interaction.
- Provided structural rationale for rapamycin-dependent and rapamycin-independent effects observed in mutants of FRAP and related ataxia-telangiectasia family homologs.
Cite This Study
Choi et al. (1996) studied this question.