2. Academic Validation
  3. Insulin-like growth factor type I selectively binds to G-quadruplex structures

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

  • Biochim Biophys Acta Gen Subj. 2019 Jan;1863(1):31-38. doi: 10.1016/j.bbagen.2018.09.022.
Hongbo Chen 1,  Hongxia Sun 2,  Yahong Chai 1,  Suge Zhang 1,  Aijiao Guan 3,  Qian Li 3,  Li Yao 4,  Yalin Tang 5
Affiliations

Affiliations

  • 1 Beijing 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.
  • 2 Beijing 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. Electronic address: [email protected].
  • 3 Beijing 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.
  • 4 Beijing 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. Electronic address: [email protected].
  • 5 Beijing 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. Electronic address: [email protected].
PMID: 30278241 DOI: 10.1016/j.bbagen.2018.09.022
Abstract

Background: G-quadruplex has been viewed as a promising therapeutic target in oncology due to its potentially important roles in physiological and pathological processes. Emerging evidence suggests that the biological functions of G-quadruplexes are closely related to the binding of some proteins. Insulin-like growth factor type I (IGF-1), as a significant modulator of cell growth and development, may serve as a quadruplex-binding protein.

Methods: The binding affinity and selectivity of IGF-1 to different DNA motifs in solution were measured by using fluorescence spectroscopy, Surface Plasmon Resonance (SPR), and force-induced remnant magnetization (FIRM). The effects of IGF-1 on the formation and stability of G-quadruplex structures were evaluated by circular dichroism (CD) and melting fluorescence resonance energy transfer (FRET) spectroscopy. The influence of quadruplex-specific ligands on the binding of G-quadruplexes with IGF-1 was determined by FIRM.

Results: IGF-1 shows a binding specificity for G-quadruplex structures, especially the G-quadruplex structure with a parallel topology. The quadruplex-specific ligands TMPyP4 and PDS (Pyridostatin) can inhibit the interaction between G-quadruplexes and proteins.

Conclusions: IGF-1 is demonstrated to selectively bind with G-quadruplex structures. The use of quadruplex-interactive ligands could modulate the binding of IGF-1 to G-quadruplexes.

General significance: This study provides us with a new perspective to understand the possible physiological relationship between IGF-1 and G-quadruplexes and also conveys a strategy to regulate the interaction between G-quadruplex DNA and proteins.

Keywords

DNA G-quadruplexes; IGF-1; Interaction; Protein; Quadruplex-ligands.

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