Surface sites for engineering allosteric control in proteins

Jeeyeon Lee, Madhusudan Natarajan, Vishal C. Nashine, Michael Socolich, Tina Vo, William P. Russ, Stephen J. Benkovic, Rama Ranganathan

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites.

Original languageEnglish (US)
Pages (from-to)438-442
Number of pages5
JournalScience
Volume322
Issue number5900
DOIs
StatePublished - Oct 17 2008

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Allosteric Site
Tetrahydrofolate Dehydrogenase
Proteins
Light
Escherichia coli Proteins
Amino Acids

ASJC Scopus subject areas

  • General

Cite this

Lee, J., Natarajan, M., Nashine, V. C., Socolich, M., Vo, T., Russ, W. P., ... Ranganathan, R. (2008). Surface sites for engineering allosteric control in proteins. Science, 322(5900), 438-442. https://doi.org/10.1126/science.1159052

Surface sites for engineering allosteric control in proteins. / Lee, Jeeyeon; Natarajan, Madhusudan; Nashine, Vishal C.; Socolich, Michael; Vo, Tina; Russ, William P.; Benkovic, Stephen J.; Ranganathan, Rama.

In: Science, Vol. 322, No. 5900, 17.10.2008, p. 438-442.

Research output: Contribution to journalArticle

Lee, J, Natarajan, M, Nashine, VC, Socolich, M, Vo, T, Russ, WP, Benkovic, SJ & Ranganathan, R 2008, 'Surface sites for engineering allosteric control in proteins', Science, vol. 322, no. 5900, pp. 438-442. https://doi.org/10.1126/science.1159052
Lee J, Natarajan M, Nashine VC, Socolich M, Vo T, Russ WP et al. Surface sites for engineering allosteric control in proteins. Science. 2008 Oct 17;322(5900):438-442. https://doi.org/10.1126/science.1159052
Lee, Jeeyeon ; Natarajan, Madhusudan ; Nashine, Vishal C. ; Socolich, Michael ; Vo, Tina ; Russ, William P. ; Benkovic, Stephen J. ; Ranganathan, Rama. / Surface sites for engineering allosteric control in proteins. In: Science. 2008 ; Vol. 322, No. 5900. pp. 438-442.
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