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Protein switches

Publication ,  Journal Article
Christensen, T; Hassouneh, W; Callahan, DJ; Chilkoti, A
January 1, 2012

Many essential cellular processes rely on naturally evolved protein switches that react in response to a particular signal, including up- and downregulation of gene expression, cell signaling processes, and allosteric enzymatic reactions. Most of these reactions are reversible and are controlled by various feedback systems; the protein undergoes a conformational change after encountering a specific trigger molecule, with the resulting structural change modifying either the activity of the affected domain or the activity of other protein domains. For example, bacteria need only expend energy producing lactose-metabolizing enzymes when lactose is present. The lac repressor (LacI) binds constitutively to the operator of the lac operon, preventing RNA polymerase binding and transcription of these lactose-metabolizing genes. The presence of lactose results in a binding event between allolactose and LacI that induces a conformational change in LacI, reducing its affinity for the DNA and allowing transcription to go forward. This simple and well-known example illustrates the essential natural function of a protein switch – to translate a signal (ligand binding) into an appropriate response (release of LacI from the DNA, thus allowing gene transcription) through a conformational change. Engineers would like to develop analogous protein switches for use as biosensors or therapeutics based on their ability to transduce specific signals into a desired response. This chapter explores the methods that have been used to create novel protein switches, the protein folding principles that enable those switches to work, and the potential applications of engineered protein switches. Engineered protein switches respond to triggers that includes....

Duke Scholars

DOI

Publication Date

January 1, 2012

Volume

3

Start / End Page

238 / 266
 

Citation

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Christensen, T., Hassouneh, W., Callahan, D. J., & Chilkoti, A. (2012). Protein switches, 3, 238–266. https://doi.org/10.1016/B978-0-12-374920-8.00316-7
Christensen, T., W. Hassouneh, D. J. Callahan, and A. Chilkoti. “Protein switches” 3 (January 1, 2012): 238–66. https://doi.org/10.1016/B978-0-12-374920-8.00316-7.
Christensen T, Hassouneh W, Callahan DJ, Chilkoti A. Protein switches. 2012 Jan 1;3:238–66.
Christensen, T., et al. Protein switches. Vol. 3, Jan. 2012, pp. 238–66. Scopus, doi:10.1016/B978-0-12-374920-8.00316-7.
Christensen T, Hassouneh W, Callahan DJ, Chilkoti A. Protein switches. 2012 Jan 1;3:238–266.

DOI

Publication Date

January 1, 2012

Volume

3

Start / End Page

238 / 266