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Insulin-like growth factor type I selectively binds to G-quadruplex structures

Hongbo Chen1, Hongxia Sun2, Yahong Chai1

  • 1Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing 100190, PR China; University of Chinese Academy of Sciences, Yuquan Road 19(A), Shijingshan District 100049, Beijing, PR China.

Biochimica Et Biophysica Acta. General Subjects
|October 3, 2018
PubMed
Abstract

Insights

Insulin-like growth factor type I (IGF-1) selectively binds to G-quadruplex DNA structures. Quadruplex-specific ligands can regulate this interaction, offering therapeutic potential in oncology.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • G-quadruplexes are crucial in cellular processes and are promising oncology targets.
  • Protein binding influences G-quadruplex biological functions.
  • Insulin-like growth factor type I (IGF-1) is a potential G-quadruplex-binding protein due to its role in cell growth.

Purpose of the Study:

  • To investigate the binding affinity and selectivity of IGF-1 to G-quadruplex DNA.
  • To evaluate the impact of IGF-1 on G-quadruplex formation and stability.
  • To explore the modulation of IGF-1 and G-quadruplex interaction by specific ligands.

Main Methods:

  • Fluorescence spectroscopy, Surface Plasmon Resonance (SPR), and force-induced remnant magnetization (FIRM) assessed binding.
  • Circular dichroism (CD) and melting FRET spectroscopy evaluated structural effects.
  • FIRM determined the influence of quadruplex ligands on protein-DNA interaction.

Main Results:

  • IGF-1 demonstrated specific binding to G-quadruplex structures, particularly those with parallel topology.
  • Quadruplex-specific ligands, TMPyP4 and PDS (Pyridostatin), inhibited IGF-1 G-quadruplex binding.
  • IGF-1 binding to G-quadruplexes was confirmed as selective.

Conclusions:

  • IGF-1 selectively binds to G-quadruplex DNA structures.
  • Quadruplex-interactive ligands can modulate IGF-1 binding to G-quadruplexes.
  • This interaction offers a strategy for regulating G-quadruplex DNA and protein interactions.
Keywords:
DNA G-quadruplexesIGF-1InteractionProteinQuadruplex-ligands

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