Linked Life Data

20471402

Source:http://linkedlifedata.com/resource/pubmed/id/20471402

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-7-12
pubmed:abstractText
Survival of organisms in dynamic environments requires accurate perception and integration of signals. At the molecular level, signal detection is mediated by signal receptor proteins that largely are of modular composition. Sensor modules, such as the widespread Per-ARNT-Sim (PAS) domains, detect signals and, in response, regulate the biological activity of effector modules. Here, we exploit the modularity of signal receptors to design and engineer synthetic receptors that comprise two PAS sensor domains responsive to different signals, and we use these signals to control the activity of a histidine kinase effector. Designed two-input PAS receptors detected oxygen and blue light in a positive cooperative manner. The extent of the response to the signals was dictated by domain topology: the dominant regulatory effect was exerted by the PAS domain proximal to the effector domain. The presence of one sensor domain modulated the signal response function of the other. Sequence and structural data on natural receptors with tandem PAS domains show that these are predominantly linked by short amphipathic alpha-helices. Signals from multiple sensor domains could be integrated and propagated to the effector domain as torques. Our results inform the rational design of receptors that integrate multiple signals to modulate cellular behavior.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
400
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
477-86
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Addition at the molecular level: signal integration in designed Per-ARNT-Sim receptor proteins.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. moeglich@uchicago.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural