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

Jixun Dai, Ding Chen, Roger A. Jones, Laurence H. Hurley, Danzhou Yang

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

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 G3 NG3 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.

Original languageEnglish (US)
Pages (from-to)5133-5144
Number of pages12
JournalNucleic acids research
Volume34
Issue number18
DOIs
StatePublished - Oct 15 2006

ASJC Scopus subject areas

  • Genetics

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