کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5371004 | 1503930 | 2013 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Detailed kinetic analysis of the interaction between the FOXO4-DNA-binding domain and DNA Detailed kinetic analysis of the interaction between the FOXO4-DNA-binding domain and DNA](/preview/png/5371004.png)
- Interaction between FOXO4 and DNA is described using a conformational change model.
- FOXO4-DBD undergoes a conformational change upon binding to the DNA.
- Segmental dynamics of FOXO4-DBD is reduced upon binding to the DNA.
- Non-specific contacts are important for binding affinity and specificity of FOXO4.
The FOXO forkhead transcription factors are potent transcriptional activators involved in a wide range of key biological processes. In this work, the real-time kinetics of the interaction between the FOXO4-DNA binding domain (FOXO4-DBD) and the DNA was studied by using surface plasmon resonance (SPR). SPR analysis revealed that the interaction between FOXO4-DBD and the double stranded DNA containing either the insulin-responsive or the Daf-16 family member-binding element is preferably described by using a conformational change model which suggests a structural change of FOXO4-DBD upon binding to the DNA. This was further confirmed by using the time-resolved tryptophan fluorescence anisotropy decay measurements which revealed profound reduction of segmental dynamics of FOXO4-DBD upon the complex formation. Alanine scanning of amino acid residues engaged in polar contacts with the DNA showed that certain non-specific contacts with the DNA backbone are very important for both the binding affinity and the binding specificity of FOXO4-DBD.
Journal: Biophysical Chemistry - Volume 184, 31 December 2013, Pages 68-78