Engineering extrinsic disorder to control protein activity in living cells

Onur Dagliyan, Miroslaw Tarnawski, Pei Hsuan Chu, David Shirvanyants, Ilme Schlichting, Nikolay Dokholyan, Klaus M. Hahn

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Optogenetic and chemogenetic control of proteins has revealed otherwise inaccessible facets of signaling dynamics. Here, we use light- or ligand-sensitive domains to modulate the structural disorder of diverse proteins, thereby generating robust allosteric switches. Sensory domains were inserted into nonconserved, surface-exposed loops that were tight and identified computationally as allosterically coupled to active sites. Allosteric switches introduced into motility signaling proteins (kinases, guanosine triphosphatases, and guanine exchange factors) controlled conversion between conformations closely resembling natural active and inactive states, as well asmodulated themorphodynamics of living cells.Our results illustrate a broadly applicable approach to design physiological protein switches.

Original languageEnglish (US)
Pages (from-to)1441-1444
Number of pages4
JournalScience
Volume354
Issue number6318
DOIs
StatePublished - Dec 16 2016

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Molecular Motor Proteins
Optogenetics
Proteins
Guanosine
Guanine
Protein Kinases
Catalytic Domain
Ligands
Light

All Science Journal Classification (ASJC) codes

  • General

Cite this

Dagliyan, O., Tarnawski, M., Chu, P. H., Shirvanyants, D., Schlichting, I., Dokholyan, N., & Hahn, K. M. (2016). Engineering extrinsic disorder to control protein activity in living cells. Science, 354(6318), 1441-1444. https://doi.org/10.1126/science.aah3404
Dagliyan, Onur ; Tarnawski, Miroslaw ; Chu, Pei Hsuan ; Shirvanyants, David ; Schlichting, Ilme ; Dokholyan, Nikolay ; Hahn, Klaus M. / Engineering extrinsic disorder to control protein activity in living cells. In: Science. 2016 ; Vol. 354, No. 6318. pp. 1441-1444.
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Dagliyan, O, Tarnawski, M, Chu, PH, Shirvanyants, D, Schlichting, I, Dokholyan, N & Hahn, KM 2016, 'Engineering extrinsic disorder to control protein activity in living cells', Science, vol. 354, no. 6318, pp. 1441-1444. https://doi.org/10.1126/science.aah3404

Engineering extrinsic disorder to control protein activity in living cells. / Dagliyan, Onur; Tarnawski, Miroslaw; Chu, Pei Hsuan; Shirvanyants, David; Schlichting, Ilme; Dokholyan, Nikolay; Hahn, Klaus M.

In: Science, Vol. 354, No. 6318, 16.12.2016, p. 1441-1444.

Research output: Contribution to journalArticle

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Dagliyan O, Tarnawski M, Chu PH, Shirvanyants D, Schlichting I, Dokholyan N et al. Engineering extrinsic disorder to control protein activity in living cells. Science. 2016 Dec 16;354(6318):1441-1444. https://doi.org/10.1126/science.aah3404