CHARACTERIZATION OF THE RECEPTOR-BINDING DOMAIN OF TETANUS TOXIN

The carboxyl-terminal half of the heavy chain of tetanus toxin (H(C)) contains the domain required for binding to purified gangliosides and neuronal cells. The structural requirements for the interaction of H(C ) with receptor were studied by generating mutants of H(C) with deleti ons at either the carboxyl or amino terminus and characterizing their binding. A deletion of 10 or more amino acids from the carboxyl termin us resulted in a major loss of H(C) binding to purified gangliosides a nd spinal cord neuronal cells, whereas a deletion of the carboxyl-term inal 5 amino acids did not affect binding. The removal of up to 263 am ino acids from the amino terminus did not inhibit binding. Each of the truncated proteins was much more sensitive to trypsin than was full-l ength H(C), suggesting an alteration in conformation. The receptor bin ding activity of H(C) was not retained in a peptide corresponding to t he carboxyl-terminal 20 amino acids. These data suggest that the carbo xyl-terminal region of H(C) is important for maintaining a conformatio n necessary for binding to receptor.