2L88

Solution structure of all parallel G-quadruplex formed by the oncogene RET promoter sequence

Summary for 2L88

• Entry DOI: 10.2210/pdb2l88/pdb
• Related: 2F8U
• NMR Information: BMRB: 17397
• Descriptor: 5'-D(*GP*GP*GP*GP*CP*GP*GP*GP*GP*CP*GP*GP*GP*GP*CP*GP*GP*GP*GP*T)-3' (1 entity in total)
• Functional Keywords: g-quadruplex, ret, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 6394.07

Authors

Tong, X.,Cao, C. (deposition date: 2011-01-06, release date: 2011-05-25, Last modification date: 2024-05-15)

Primary citation

Tong, X.,Lan, W.,Zhang, X.,Wu, H.,Liu, M.,Cao, C.
Solution structure of all parallel G-quadruplex formed by the oncogene RET promoter sequence
Nucleic Acids Res., 39:6753-6763, 2011

PubMed Abstract: RET protein functions as a receptor-type tyrosine kinase and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the promoter plays an important role in the transcriptional regulation of RET. 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. The overall G-quadruplex is composed of three stacked G-tetrad and four syn guanines, which shows distinct features for all parallel-stranded folding topology. The core structure contains one G-tetrad with all syn guanines and two other with all anti-guanines. There are three double-chain reversal loops: the first and the third loops are made of 3 nt G-C-G segments, while the second one contains only 1 nt C10. These loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure and their conformations are in accord with the experimental mutations. The distinct RET promoter G-quadruplex structure suggests that it can be specifically involved in gene regulation and can be an attractive target for pathway-specific drug design.

PubMed: 21540209
DOI: 10.1093/nar/gkr233

Experimental method

SOLUTION NMR