2f8u: Difference between revisions
New page: left|200px<br /><applet load="2f8u" size="350" color="white" frame="true" align="right" spinBox="true" caption="2f8u" /> '''Solution structure of G-quadruplex formed in... |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
BCL2 protein functions as an inhibitor of cell apoptosis and has been | BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the P1 promoter plays an important role in the transcriptional regulation of BCL2. 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. This well-defined mixed parallel/antiparallel-stranded G-quadruplex structure contains three G-tetrads of mixed G-arrangements, which are connected with two lateral loops and one side loop, and four grooves of different widths. The three loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure. The loop conformations are in accord with the experimental mutation and footprinting data. The first 3-nt loop adopts a lateral loop conformation and appears to determine the overall folding of the BCL2 G-quadruplex. The third 1-nt double-chain-reversal loop defines another example of a stable parallel-stranded structural motif using the G3NG3 sequence. Significantly, the distinct major BCL2 promoter G-quadruplex structure suggests that it can be specifically involved in gene modulation and can be an attractive target for pathway-specific drug design. | ||
==About this Structure== | ==About this Structure== | ||
| Line 21: | Line 21: | ||
[[Category: nmr]] | [[Category: nmr]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:18:53 2008'' | ||
Revision as of 18:18, 21 February 2008
|
Solution structure of G-quadruplex formed in the human Bcl-2 promoter
OverviewOverview
BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the P1 promoter plays an important role in the transcriptional regulation of BCL2. 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. This well-defined mixed parallel/antiparallel-stranded G-quadruplex structure contains three G-tetrads of mixed G-arrangements, which are connected with two lateral loops and one side loop, and four grooves of different widths. The three loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure. The loop conformations are in accord with the experimental mutation and footprinting data. The first 3-nt loop adopts a lateral loop conformation and appears to determine the overall folding of the BCL2 G-quadruplex. The third 1-nt double-chain-reversal loop defines another example of a stable parallel-stranded structural motif using the G3NG3 sequence. Significantly, the distinct major BCL2 promoter G-quadruplex structure suggests that it can be specifically involved in gene modulation and can be an attractive target for pathway-specific drug design.
About this StructureAbout this Structure
2F8U is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
ReferenceReference
NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region., Dai J, Chen D, Jones RA, Hurley LH, Yang D, Nucleic Acids Res. 2006;34(18):5133-44. Epub 2006 Sep 22. PMID:16998187
Page seeded by OCA on Thu Feb 21 17:18:53 2008