TY - JOUR
T1 - Engineering extrinsic disorder to control protein activity in living cells
AU - Dagliyan, Onur
AU - Tarnawski, Miroslaw
AU - Chu, Pei Hsuan
AU - Shirvanyants, David
AU - Schlichting, Ilme
AU - Dokholyan, Nikolay V.
AU - Hahn, Klaus M.
N1 - Publisher Copyright:
Copyright 2016 by the American Association for the Advancement of Science; all rights reserved.
PY - 2016/12/16
Y1 - 2016/12/16
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aah3404
DO - 10.1126/science.aah3404
M3 - Article
C2 - 27980211
AN - SCOPUS:85006320532
SN - 0036-8075
VL - 354
SP - 1441
EP - 1444
JO - Science
JF - Science
IS - 6318
ER -