Emerging Principles of Post-Receptor Signal Transduction

Conclusion Emerging Principles of Post-Receptor Signal Transduction 

Ligand-Induced Receptor Activation Re-orientation of Intracellular Domains into Closer Proximity for Signaling 

Receptor pre-assembly has also been described for other receptor families and appears to be a fundamental principle for the signal transduction of oligomeric receptors. For example, the insulin receptor is a 

Whether or not transmembrane helix rotation is a crucial event that leads to receptor activation in the case of TNER superfamily, a net effect of ligand binding and receptor activation appears to be the induced closer proximity of the intracellular domains (Eig. 12A), as shovm by fluorescence energy transfer experiments (Ghan et al, 2000). In the structures of TRAF-receptor complexes, the distance between bound receptor peptides is approximately 50 A. This suggests that a distance of separation between the intracellular domains of receptor chains on the order of 50 A may be optimal for TRAP recruitment and signaling transduction. 

This oligomeric TRAF-receptor interaction geometry provides avidity to increase the affinity of TRAP recruitment upon receptor activation. This is necessary because interactions between TRAFs and monomeric receptors are relatively weak (Table III), which ensures that TRAFs do not 

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Conclusion Emerging Principles of Post-Receptor Signal Transduction. 265... 

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