Effects of Diabetes Insipidus Mutations on Neurophysin Folding and Function Academic Article uri icon


MeSH Major

  • Diabetes Insipidus
  • Neurophysins


  • Mechanisms underlying the pathogenicity of diabetes insipidus mutations were probed by studying their effects on the properties of bovine oxytocin-related neurophysin. The mutations G17V, DeltaE47, G57S, G57R, and C67STOP were each shown to have structural consequences that would diminish the conformational stability and folding efficiency of the precursors in which they were incorporated, and factors contributing to the origins of these property changes were identified. Effects of the mutations on dimerization of the folded proteins were similarly analyzed. The projected relative impact of the above mutations on precursor folding properties qualitatively parallels the reported relative severity of their effects on the biological handling of the human vasopressin precursor, but quantitative differences between thermodynamic effects and biological impact are noted and explored. The sole mutation for which no clear thermodynamic basis was found for its pathogenicity was 87STOP, suggesting that the region of the precursor deleted by this mutation plays a role in targeting independent from effects on folding, or participates in stabilizing interactions unique to the human vasopressin precursor.

publication date

  • August 10, 2001



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M103477200

PubMed ID

  • 11395505

Additional Document Info

start page

  • 29671

end page

  • 80


  • 276


  • 32