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Design and signaling mechanism of light‐regulated histidine kinases
Author(s) -
Möglich Andreas,
Ayers Rebecca A,
Moffat Keith
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb275
Subject(s) - histidine kinase , kinase , protein kinase domain , histidine , microbiology and biotechnology , signal transduction , effector , phosphorylation , fusion protein , coiled coil , biology , linker , biophysics , chemistry , biochemistry , gene , enzyme , computer science , recombinant dna , mutant , operating system
Signal transduction proteins are organized into sensor (input) domains that perceive a signal and, in response, regulate the biological activity of effector (output) domains. We reprogrammed the input signal specificity of a normally oxygen‐sensitive, light‐inert histidine kinase by replacing its chemosensor domain by a light‐oxygen‐voltage (LOV) photosensor domain. Illumination of the resultant fusion kinase YF1 reduced net kinase activity by ~1000‐fold in vitro. YF1 also controls gene expression in a light‐dependent manner in vivo. Signals are transmitted from the LOV sensor domain to the histidine kinase domain via a 40‐60º rotational movement within an α‐helical coiled coil linker; light is acting as a rotary switch. These signaling principles are broadly applicable to domains linked by α‐helices, and to both chemo‐ and photosensors. Conserved sequence motifs guide the rational design of light‐regulated variants of histidine kinases and other proteins. Funded by NIH grant GM036452 to K.M.