2M4P

Solution structure of an intramolecular propeller-type G-quadruplex containing a single bulge

Summary for 2M4P

• Entry DOI: 10.2210/pdb2m4p/pdb
• NMR Information: BMRB: 19017
• Descriptor: DNA (5'-D(*TP*TP*GP*TP*GP*GP*TP*GP*GP*GP*TP*GP*GP*GP*TP*GP*GP*GP*T)-3') (1 entity in total)
• Functional Keywords: g-quadruplex, bulges, dna
• Total number of polymer chains: 1
• Total formula weight: 6034.86

Authors

Mukundan, V.T.,Phan, A.T. (deposition date: 2013-02-08, release date: 2013-06-19, Last modification date: 2024-05-15)

Primary citation

Mukundan, V.T.,Phan, A.T.
Bulges in G-Quadruplexes: Broadening the Definition of G-Quadruplex-Forming Sequences.
J.Am.Chem.Soc., 135:5017-5028, 2013

PubMed Abstract: We report on the first solution structure of an intramolecular G-quadruplex containing a single bulge and present evidence for extensive occurrence of bulges in different G-quadruplex contexts. The NMR solution structure of the d(TTGTGGTGGGTGGGTGGGT) sequence reveals a propeller-type parallel-stranded G-quadruplex containing three G-tetrad layers, three double-chain-reversal loops, and a bulge. All guanines participate in the formation of the G-tetrad core, despite the interruption between the first guanine and the next two guanines by a thymine, which forms a single-residue bulge and is projected out of the G-tetrad core. To provide a more general understanding about the formation of bulges within G-quadruplexes, we systematically investigated the effects of the residue type, the size, the position, and the number of bulges on the structure and stability of G-quadruplexes. The formation of bulges has also been observed in two different G-quadruplex scaffolds with different strand orientations and folding topologies. Our results show that bulges can be formed in many different situations within G-quadruplexes. While many sequences tested in this study can form stable G-quadruplex structures, all of them defy the description of sequences G3+NL1G3+NL2G3+NL3G3+, currently used in most bioinformatics searches for identifying potential G-quadruplex-forming sequences in the genomes. Broadening of this description to include the possibilities of bulge formation should allow the identification of more G-quadruplex-forming sequences which went unnoticed in the earlier searches. This study could also open the possibilities of exploiting bulges as recognition elements for interactions between G-quadruplexes and other molecules.

PubMed: 23521617
DOI: 10.1021/ja310251r

Experimental method

SOLUTION NMR