Protein memory through altered folding mediated by intramolecular chaperones

Ujwal Shinde, J. J. Liu, M. Inouye

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

The 77-residue propeptide of subtilisin acts as an intramolecular chaperone that organizes the correct folding of its own protease domain. Similar folding mechanisms are used by several prokaryotic and eukaryotic proteins, including prohormone-convertases. Here we show that the intramolecular chaperone of subtilisin facilitates folding by acting as a template for its protease domain, although it does not form part of that domain. Subtilisin E folded by an intramolecular chaperone with an Ile(-48)- to-Val mutation acquires an 'altered' enzymatically active conformation that differs from wild-type subtilisin E. Although both the altered and wild-type subtilisins have identical amino-acid sequences, as determined by amino- terminal sequencing and mass spectrometry, they bind their cognate intramolecular chaperones with 4.5-fold greater affinity than non-cognate intramolecular chaperones, when added in trans. The two subtilisins also have different secondary structures, thermostability and substrate specificities. Our results indicate that an identical polypeptide can fold into an altered conformation through a mutated intramolecular chaperone and maintains memory of the folding process. Such a phenomenon, which we term 'protein memory', may be important in investigations of protein folding.

Original languageEnglish (US)
Pages (from-to)520-522
Number of pages3
JournalNature
Volume389
Issue number6650
DOIs
StatePublished - 1997
Externally publishedYes

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Subtilisins
Subtilisin
Proteins
Peptide Hydrolases
Proprotein Convertases
Protein Folding
Substrate Specificity
Amino Acid Sequence
Mass Spectrometry
Peptides
Mutation

ASJC Scopus subject areas

  • General

Cite this

Protein memory through altered folding mediated by intramolecular chaperones. / Shinde, Ujwal; Liu, J. J.; Inouye, M.

In: Nature, Vol. 389, No. 6650, 1997, p. 520-522.

Research output: Contribution to journalArticle

Shinde, Ujwal ; Liu, J. J. ; Inouye, M. / Protein memory through altered folding mediated by intramolecular chaperones. In: Nature. 1997 ; Vol. 389, No. 6650. pp. 520-522.
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