Conformation limited proteolysis in the common neurophysin-copeptin precursor shown by trypsin-sepharose chromatographic proteolysis.

The guinea pig two-domain precursor of MSEL-neurophysin and copeptin has been passed through a trypsin-Sepharose column in order to mimic the enzyme processing by a membrane-bound endopeptidase. Only two cleavages were observed located in the inter-domain sequence (at Arg-94 and Arg-98), in contrast to several additional cleavages found when free neurophysin or copeptin is subjected to soluble trypsin. Because the physiological maturation involves a single cleavage at Arg-94, both local accessibility in the precursor and narrow specificity of the enzyme are implied in the processing.