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Engineering extrinsic disorder to control protein activity in living cells.

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 as modulated the morphodynamics of living cells. Our results illustrate a broadly applicable approach to design physiological protein switches.

SUBMITTER: Dagliyan O

PROVIDER: S-EPMC5362825 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Engineering extrinsic disorder to control protein activity in living cells.

Dagliyan Onur O Tarnawski Miroslaw M Chu Pei-Hsuan PH Shirvanyants David D Schlichting Ilme I Dokholyan Nikolay V NV Hahn Klaus M KM

Science (New York, N.Y.) 20161201 6318

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 ...[more]

PMID: 27980211

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