Global suppression of protein folding defects and inclusion body formation

Anna Mitraki, Bentley A Fane, Cameron Haase-Pettingell, Julian Sturtevant, Jonathan King

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

Amino acid substitutions at a site in the center of the bacteriophage protein P22 tailspike polypeptide chain suppress temperature-sensitive folding mutations at many sites throughout the chain. Characterization of the intracellular folding and chain assembly process reveals that the suppressors act in the folding pathway, inhibiting the aggregation of an early folding intermediate into the kinetically trapped inclusion body state. The suppressors alone increase the folding efficiency of the otherwise wild-type polypeptide chain without altering the stability or activity of the native state. These amino acid substitutions identify an unexpected aspect of the protein folding grammar-sequences within the chain that carry information inhibiting unproductive off-pathway conformations. Such mutations may serve to increase the recovery of protein products of cloned genes.

Original languageEnglish (US)
Pages (from-to)54-58
Number of pages5
JournalScience
Volume253
Issue number5015
StatePublished - Jul 5 1991
Externally publishedYes

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Inclusion Bodies
Protein Folding
Amino Acid Substitution
Bacteriophage P22
Peptides
Mutation
Proteins
Temperature

ASJC Scopus subject areas

  • General

Cite this

Mitraki, A., Fane, B. A., Haase-Pettingell, C., Sturtevant, J., & King, J. (1991). Global suppression of protein folding defects and inclusion body formation. Science, 253(5015), 54-58.

Global suppression of protein folding defects and inclusion body formation. / Mitraki, Anna; Fane, Bentley A; Haase-Pettingell, Cameron; Sturtevant, Julian; King, Jonathan.

In: Science, Vol. 253, No. 5015, 05.07.1991, p. 54-58.

Research output: Contribution to journalArticle

Mitraki, A, Fane, BA, Haase-Pettingell, C, Sturtevant, J & King, J 1991, 'Global suppression of protein folding defects and inclusion body formation', Science, vol. 253, no. 5015, pp. 54-58.
Mitraki A, Fane BA, Haase-Pettingell C, Sturtevant J, King J. Global suppression of protein folding defects and inclusion body formation. Science. 1991 Jul 5;253(5015):54-58.
Mitraki, Anna ; Fane, Bentley A ; Haase-Pettingell, Cameron ; Sturtevant, Julian ; King, Jonathan. / Global suppression of protein folding defects and inclusion body formation. In: Science. 1991 ; Vol. 253, No. 5015. pp. 54-58.
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