Insulin-like growth factor type I selectively binds to G-quadruplex structures.
Aminoquinolines
/ chemistry
Circular Dichroism
DNA, Single-Stranded
/ chemistry
Fluorescence Resonance Energy Transfer
G-Quadruplexes
Humans
Insulin-Like Growth Factor I
/ chemistry
Ligands
Magnetics
Oligonucleotides
/ chemistry
Picolinic Acids
/ chemistry
Protein Binding
Spectrometry, Fluorescence
Surface Plasmon Resonance
DNA G-quadruplexes
IGF-1
Interaction
Protein
Quadruplex-ligands
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
20
06
2018
revised:
26
09
2018
accepted:
27
09
2018
pubmed:
3
10
2018
medline:
17
8
2019
entrez:
3
10
2018
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 30278241
pii: S0304-4165(18)30310-6
doi: 10.1016/j.bbagen.2018.09.022
pii:
doi:
Substances chimiques
Aminoquinolines
0
DNA, Single-Stranded
0
IGF1 protein, human
0
Ligands
0
Oligonucleotides
0
Picolinic Acids
0
pyridostatin
0
Insulin-Like Growth Factor I
67763-96-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
31-38Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.