Journal article
The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals
Nature structural & molecular biology, Vol.20(7), pp.876-883
07/2013
DOI: 10.1038/nsmb.2595
PMCID: PMC3702670
PMID: 23728292
Abstract
Glucocorticoid receptor binds to genomic response elements and regulates gene transcription with cell- and gene-specificity. Within a response element, the precise sequence to which the receptor binds has been implicated in directing its structure and activity. We use NMR chemical shift difference mapping to show that non-specific interactions with particular base positions within the binding sequence, such as those of the “spacer”, affect the conformation of distinct regions of the rat glucocorticoid receptor DNA binding domain. These regions include the DNA-binding surface, the “lever arm” and the dimerization interface, suggesting an allosteric pathway that signals between the DNA binding sequence and the associated dimer partner. Disrupting this path by mutating the dimer interface alters sequence-specific conformations, DNA-binding kinetics and transcriptional activity. Our study demonstrates that glucocorticoid receptor dimer partners collaborate to read DNA shape and to direct sequence specific gene activity.
Details
- Title: Subtitle
- The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals
- Creators
- Lisa C Watson - Tetrad Graduate Program, University of California, San Francisco, San Francisco, California, USAKristopher M Kuchenbecker - Biophysics Graduate Group, University of California, San Francisco, San Francisco, California, USABenjamin J Schiller - Tetrad Graduate Program, University of California, San Francisco, San Francisco, California, USAJohn D Gross - Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USAMiles A Pufall - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USAKeith R Yamamoto - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA
- Resource Type
- Journal article
- Publication Details
- Nature structural & molecular biology, Vol.20(7), pp.876-883
- DOI
- 10.1038/nsmb.2595
- PMID
- 23728292
- PMCID
- PMC3702670
- NLM abbreviation
- Nat Struct Mol Biol
- ISSN
- 1545-9993
- eISSN
- 1545-9985
- Language
- English
- Date published
- 07/2013
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984025394702771
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