Folding Pathway Mediated by an Intramolecular Chaperone: Characterization of the Structural Changes in Pro-subtilisin E Coincident with Autoprocess ing

Ujwal Shinde, Masayori Inouye

Research output: Contribution to journalEditorial

52 Scopus citations

Abstract

Mechanisms by which many N-terminal propeptides facilitate folding of proteins are unknown. The maturation of such proteins from their precursors involve three stepps, namely: (1) folding of the precursor, (2) autoprocessing of the propeptide from the N terminus and (3) degradation of the cleaved propeptide. Using subtilisin E we have analyzed the mechanism of propeptide-mediated protein folding. Two active site mutations allow us to trap intermediates at stages of autoprocessing and degradation. An analysis of these intermediates has shown the existence of a molten-globule-like intermediate on the folding pathway. After autoprocessing of the propeptide, this intermediate undergoes a structural reorganization which reduces solvent-accessible hydrophobic surface area and increases the amount of its tertiary structure. Removal of the propeptide from the mature enzyme in this intermediate state occurs only by proteolytic degradation and contributes to the stability of the active enzyme.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalJournal of molecular biology
Volume252
Issue number1
DOIs
StatePublished - Sep 8 1995

Keywords

  • autoprocessing
  • intramolecular chaperones
  • molten globule intermediates
  • protein folding
  • subtilisin

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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