期刊
NUCLEIC ACIDS RESEARCH
卷 39, 期 15, 页码 6753-6763出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkr233
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资金
- National Basic Research Program of China [2009CB918600, 2011CB966300]
- National Science Foundation of China [30800176, 20872169, 20921091]
- Science and Technology Commission of Shanghai Municipality, China, Pujiang [08PJ1411700]
- State Key laboratory of Magnetic Resonance and Atomic and Molecular Physics
- Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, CAS [T152902]
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.
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