2M27

Major G-quadruplex structure formed in human VEGF promoter, a monomeric parallel-stranded quadruplex

Summary for 2M27

• Entry DOI: 10.2210/pdb2m27/pdb
• Related: 1XAV 2F8U 2L7V 2LBY
• NMR Information: BMRB: 18902
• Descriptor: DNA_(5'-D(*CP*GP*GP*GP*GP*CP*GP*GP*GP*CP*CP*TP*TP*GP*GP*GP*CP*GP*GP*GP*GP*T)-3')_ (1 entity in total)
• Functional Keywords: vegf promoter, g-quadruplex structure, anticancer drug target, parallel g-quadruplex, variable loop interactions, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 6922.41

Authors

Agrawal, P.,Hatzakis, E.,Guo, K.,Carver, M.,Yang, D. (deposition date: 2012-12-14, release date: 2013-09-18, Last modification date: 2024-05-15)

Primary citation

Agrawal, P.,Hatzakis, E.,Guo, K.,Carver, M.,Yang, D.
Solution structure of the major G-quadruplex formed in the human VEGF promoter in K+: insights into loop interactions of the parallel G-quadruplexes.
Nucleic Acids Res., 41:10584-10592, 2013

PubMed Abstract: Vascular endothelial growth factor (VEGF) proximal promoter region contains a poly G/C-rich element that is essential for basal and inducible VEGF expression. The guanine-rich strand on this tract has been shown to form the DNA G-quadruplex structure, whose stabilization by small molecules can suppress VEGF expression. We report here the nuclear magnetic resonance structure of the major intramolecular G-quadruplex formed in this region in K(+) solution using the 22mer VEGF promoter sequence with G-to-T mutations of two loop residues. Our results have unambiguously demonstrated that the major G-quadruplex formed in the VEGF promoter in K(+) solution is a parallel-stranded structure with a 1:4:1 loop-size arrangement. A unique capping structure was shown to form in this 1:4:1 G-quadruplex. Parallel-stranded G-quadruplexes are commonly found in the human promoter sequences. The nuclear magnetic resonance structure of the major VEGF G-quadruplex shows that the 4-nt middle loop plays a central role for the specific capping structures and in stabilizing the most favored folding pattern. It is thus suggested that each parallel G-quadruplex likely adopts unique capping and loop structures by the specific middle loops and flanking segments, which together determine the overall structure and specific recognition sites of small molecules or proteins.

PubMed: 24005038
DOI: 10.1093/nar/gkt784

Experimental method

SOLUTION NMR