NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region

Nucleic Acids Res. 2006;34(18):5133-44. doi: 10.1093/nar/gkl610. Epub 2006 Sep 22.


BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the P1 promoter plays an important role in the transcriptional regulation of BCL2. 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. This well-defined mixed parallel/antiparallel-stranded G-quadruplex structure contains three G-tetrads of mixed G-arrangements, which are connected with two lateral loops and one side loop, and four grooves of different widths. The three loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure. The loop conformations are in accord with the experimental mutation and footprinting data. The first 3-nt loop adopts a lateral loop conformation and appears to determine the overall folding of the BCL2 G-quadruplex. The third 1-nt double-chain-reversal loop defines another example of a stable parallel-stranded structural motif using the G3NG3 sequence. Significantly, the distinct major BCL2 promoter G-quadruplex structure suggests that it can be specifically involved in gene modulation and can be an attractive target for pathway-specific drug design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • DNA Mutational Analysis
  • G-Quadruplexes
  • Genes, bcl-2*
  • Guanine / chemistry*
  • Humans
  • Models, Molecular*
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation
  • Phosphorus / chemistry
  • Promoter Regions, Genetic*
  • Protons
  • Solutions
  • Transcription, Genetic


  • Protons
  • Solutions
  • Phosphorus
  • Guanine
  • DNA