Corticotropin-releasing factor affinity switch

Corticotropin-releasing factor (CRF) is an early signal of the stress response and is also an important neuromodulator of memory consolidation, anxiety, locomotor activity and food intake. In September 25 Proceedings of the National Academy of Sciences, Klaus Eckart and colleagues from the Max Planck Institute of Experimental Medicine, Goettingen, show that it is possible to selectively change the binding properties of the CRF hormone by replacing a single amino acid in the CRF structure (Proc Natl Acad Sci USA 2001, 98:11142-11147).

Eckart et al. found that an A to G or G to A change at position 22 of the human/rat CRF (h/rCRF) serves as a switch, discriminating between CRF binding protein (CRFBP) and CRF receptor (CRFR). To assess the potential of this switch, they modified the CRF antagonist astressin, and found that replacing A with G efficiently antagonized in vivo CRFR1-dependent reduction of locomotion...