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Structural Insights into the CRTC2-CREB Complex Assembly on CRE.
Yihui Song1, Liting Zhai1, Jonathan Valencia Swain1
1Key Laboratory of Nutrition and Metabolism, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, P.R. China.
Journal of Molecular Biology
|May 8, 2018
Summary
CREB coactivators (CRTCs) bind CREB and DNA to regulate gene transcription. Structural studies reveal a CRTC-CREB-DNA complex, highlighting CRTC
Area of Science:
- Molecular Biology
- Structural Biology
- Gene Regulation
Background:
- CREB is central to cAMP-mediated transcription.
- CRTCs are key coactivators in CREB-mediated transcription.
- CRTCs translocate to the nucleus to activate target genes.
Purpose of the Study:
- To elucidate the structural basis of CRTC-CREB-DNA complex formation.
- To understand the role of CRTC-DNA interactions in transcription regulation.
Main Methods:
- X-ray crystallography to determine complex structures.
- Structure-guided functional assays.
Main Results:
- Crystal structures reveal a 2:2 CRTC-CREB complex on CRE DNA.
- CRTC interacts with both CREB and DNA via conserved residues.
- CRTC-DNA interaction confers DNA shape selectivity for gene activation.
Conclusions:
- CRTC-DNA and CRTC-CREB interactions are crucial for complex assembly and CREB stabilization.
- CRTC-mediated DNA shape selectivity may regulate specific CRE gene transcription.
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