Solution structure of all parallel G-quadruplex formed by the oncogene RET promoter sequence

Nucleic Acids Res. 2011 Aug;39(15):6753-63. doi: 10.1093/nar/gkr233. Epub 2011 May 2.


RET protein functions as a receptor-type tyrosine kinase and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the promoter plays an important role in the transcriptional regulation of RET. Here, we report the NMR solution structure of the major intramolecular G-quadruplex formed on the G-rich strand of this region in K(+) solution. The overall G-quadruplex is composed of three stacked G-tetrad and four syn guanines, which shows distinct features for all parallel-stranded folding topology. The core structure contains one G-tetrad with all syn guanines and two other with all anti-guanines. There are three double-chain reversal loops: the first and the third loops are made of 3 nt G-C-G segments, while the second one contains only 1 nt C10. These loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure and their conformations are in accord with the experimental mutations. The distinct RET promoter G-quadruplex structure suggests that it can be specifically involved in gene regulation and can be an attractive target for pathway-specific drug design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • G-Quadruplexes*
  • Models, Molecular
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular
  • Potassium / chemistry
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins c-ret / genetics*


  • Proto-Oncogene Proteins c-ret
  • Potassium

Associated data

  • PDB/2L88