STRUCTURE-FUNCTION STUDIES OF HUMAN CILIARY NEUROTROPHIC FACTOR

Ciliary neurotrophic factor (CNTF) is a polypeptide that promotes the survival and/or differentiation of a number of neural cell types. Here we present a structural and functional analysis of the human CNTF mol ecule. Variant proteins were synthesized by Escherichia coli transform ed with mutant cDNA constructs, and purified by SDS-polyacrylamide gel electrophoresis and reverse phase high pressure liquid chromatography . Most variant CNTF proteins lacked neurotrophic activity, but two N-a nd C-terminal deletions (Delta 2-14 and Delta 173-200, respectively) a ctually displayed a several-fold increase in specific activity. Loss o f biological activity was accompanied by changes in the alpha-helical nature of CNTF as measured by circular dichroism. These data strengthe n the proposed similarity between CNTF and the family of hematopoietic cytokines.