6SUU

NMR structure of KRAS32R G9T conformer G-quadruplex within KRAS promoter region

6SUU の概要

• エントリーDOI: 10.2210/pdb6suu/pdb
• NMR情報: BMRB: 34431
• 分子名称: KRAS32R G9T, POTASSIUM ION (2 entities in total)
• 機能のキーワード: kras g-quadruplex, dna
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10324.77

構造登録者

Marquevielle, J.,Salgado, G. (登録日: 2019-09-16, 公開日: 2020-02-05, 最終更新日: 2024-06-19)

主引用文献

Marquevielle, J.,Robert, C.,Lagrabette, O.,Wahid, M.,Bourdoncle, A.,Xodo, L.E.,Mergny, J.L.,Salgado, G.F.
Structure of two G-quadruplexes in equilibrium in the KRAS promoter.
Nucleic Acids Res., 48:9336-9345, 2020

PubMed Abstract: KRAS is one of the most mutated oncogenes and still considered an undruggable target. An alternative strategy would consist in targeting its gene rather than the protein, specifically the formation of G-quadruplexes (G4) in its promoter. G4 are secondary structures implicated in biological processes, which can be formed among G-rich DNA (or RNA) sequences. Here we have studied the major conformations of the commonly known KRAS 32R, or simply 32R, a 32 residue sequence within the KRAS Nuclease Hypersensitive Element (NHE) region. We have determined the structure of the two major stable conformers that 32R can adopt and which display slow equilibrium (>ms) with each other. By using different biophysical methods, we found that the nucleotides G9, G25, G28 and G32 are particularly implicated in the exchange between these two conformations. We also showed that a triad at the 3' end further stabilizes one of the G4 conformations, while the second conformer remains more flexible and less stable.

PubMed: 32432667
DOI: 10.1093/nar/gkaa387

実験手法

SOLUTION NMR