2F8U

G-quadruplex structure formed in human Bcl-2 promoter, hybrid form

Summary for 2F8U

• Entry DOI: 10.2210/pdb2f8u/pdb
• Related: 1XAV 2LBY 2M27
• NMR Information: BMRB: 6975
• Descriptor: 5'-D(*GP*GP*GP*CP*GP*CP*GP*GP*GP*AP*GP*GP*AP*AP*TP*TP*GP*GP*GP*CP*GP*GP*G)-3' (1 entity in total)
• Functional Keywords: g-quadruplex, bcl-2 promoter, dna
• Total number of polymer chains: 1
• Total formula weight: 7308.68

Authors

Dai, J.,Chen, D.,Carver, M.,Yang, D. (deposition date: 2005-12-03, release date: 2006-11-07, Last modification date: 2024-05-01)

Primary citation

Dai, J.,Chen, D.,Jones, R.A.,Hurley, L.H.,Yang, D.
NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region.
Nucleic Acids Res., 34:5133-5144, 2006

PubMed 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 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.

PubMed: 16998187
DOI: 10.1093/nar/gkl610

Experimental method

SOLUTION NMR