Neurophysin–neuropeptide hormone complexes: Biosynthetic origin and noncovalent interactions

Abstract

SynopsisRecent studies of the neurophysins and associated neuropeptide hormones have addressed both the biosynthetic pathways by which these noncovalent protein-peptide complexes are derived in neurosecretory neurons and the nature of the noncovalent interactions likely to occur during transport and storage in neurosecretory granules within the neurons. In uitro translation of hypothalamic mRNA and sequencing of cDNA obtained from this mRNA have yielded chemical evidence that each complex of hormone and major neurophysin is made through a common precursor molecule. The mature complexes obtained upon proteolytic processing of precursors exhibit interdependent hormone binding and self-association interactions. Photoaffinity labeling and quantitative affinity chromatography have helped detect and define the binding surfaces involved. Further study of the structural nature of these surfaces is being carried out using large neurophysin fragments obtained by limited tryptic proteolysis.

The Hormone Domain of the Vasopressin Prohormone is Required for the Correct Prohormone Trafficking Through the Secretory Pathway

“…Before the structure of the common vasopressin‐neurophysin precursor was known, it was already indicated that correct pairing of disulphides of neurophysin in vivo would involve an interaction between vasopressin and neurophysin. After elucidation of the vasopressin precursor, it was demonstrated that noncovalent hormone–neurophysin interactions occurred within the precursors (10, 38). It was also demonstrated that the instability of the disulphides in unliganded neurophysin would prevent efficient folding, and that addition of peptide ligands that bind to neurophysin would overcome the instability (17, 22).…”