Characterizing the Biomolecular Interactions between Insulin and G-Quadruplex DNA

Abstract

The formation of guanine (G)-quadruplex structures in the guanine-rich tandem repeats of the insulin-linked polymorphic region (ILPR) is linked to transcriptional effects on the insulin gene. Recent studies demonstrate that the ILPR G-quadruplexes can bind to insulin while the energetics of this interaction with the most common ILPR repeat sequences have been characterized. Studies have also measured the transcriptional activity of less common ILPR repeats. Transcriptional activity for these repeats is significantly lower than that of the consensus sequence but can be increased substantially by varying only one or two nucleotides. To determine the potential role of G-quadruplex formation and stability in regulating transcription, we have studied the second and third most common ILPR repeats as well as their variant sequences that exhibit increased transcriptional activity. Circular dichroism (CD) spectroscopy, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC) have been used to characterize the binding interaction between insulin and each of the four ILPR repeat sequences. The bulk thermodynamic measurements performed at various temperatures from 20 - 37 degrees Celsius provide insight into these biomolecular interactions. Correction et al.Biophysical JournalApril 16, 2013In Brief2013. Characterizing the Biomolecular Interactions between Insulin and G-Quadruplex DNA. Nicole L. Michmerhuizen, Christine M. Timmer, Kumar Sinniah. Biophys. J. 104(2)s: 419a. Full-Text PDF Open Archive