Linked Life Data

16844141

Source:http://linkedlifedata.com/resource/pubmed/id/16844141

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-7-28
pubmed:abstractText
The transcription of genes encoding resistance to the antibiotic, tetracycline (Tc), is repressed by tetracycline repressor (TetR), which is a homodimeric alpha-helical protein possessing a small N-terminal DNA binding domain (DNB domain) and a larger C-terminal domain (TBD domain). Binding of Tc to the TBD domain induces a subtle conformational change in the DNB domain that leads to abrogation of its DNA-binding activity, and induction of Tc resistance. While most previous studies on TetR have focused on the effects of Tc-binding on the DNB domain conformation, here we have investigated the role of the DNB domain in modulating Tc binding. We have discovered that a TBD domain construct entirely lacking the DNB domain displays a drastic reduction in Tc-binding affinity even though the DNB domain is far from the Tc-binding site. In the context of full-length TetR, highly destabilizing amino acid substitutions in the DNB domain cause reductions in Tc-binding activity. Strikingly, the DNB domains of these mutants, which are completely unfolded in the absence of Tc, are induced to fold when Tc is bound. These results demonstrate that there is a previously unrecognized two-way interdomain signaling mechanism in TetR whereby the DNB domain is required for maximal Tc-binding by the TBD domain, and Tc-binding in the TBD domain leads to stabilization of the DNB domain. Furthermore, our work suggests that detailed thermodynamic and kinetic studies on mutant forms of other allosteric proteins may also reveal surprising and previously undetected modes of interdomain communication.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
361
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
382-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Two-way interdomain signal transduction in tetracycline repressor.
pubmed:affiliation
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't