D1 CAP REGION INVOLVED IN THE RECEPTOR RECOGNITION AND NEURAL CELL-SURVIVAL ACTIVITY OF HUMAN CILIARY NEUROTROPHIC FACTOR

Human ciliary neurotrophic factor (hCNTF), which promotes the cell sur vival and differentiation of motor and other neurons, is a protein bel onging structurally to the alpha-helical cytokine family. hCNTF was su bjected to three-dimensional structure modeling and site-directed muta genesis to analyze its structure-function relationship, The replacemen t of Lys-155 with any other amino acid residue resulted in abolishment of neural cell survival activity, and some of the Glu-153 mutant prot eins had 5- to 10-fold higher biological activity. The D1 cap region ( around the boundary between the CD loop and helix D) of hCNTF, includi ng both Glu-153 and Lys-155, was shown to play a key role in the biolo gical activity of hCNTF as one of the putative receptor-recognition si tes. In this article, the D1 cap region of the 4-helix-bundle proteins is proposed to be important in receptor recognition and biological ac tivity common to alpha-helical cytokine proteins reactive with gp130, a component protein of the receptors.