[NMR paper] High-resolution three-dimensional NMR structure of the KRAS proto-oncogene promoter reveals key features of a G-quadruplex involved in transcriptional regulation.
High-resolution three-dimensional NMR structure of the KRAS proto-oncogene promoter reveals key features of a G-quadruplex involved in transcriptional regulation.
Related ArticlesHigh-resolution three-dimensional NMR structure of the KRAS proto-oncogene promoter reveals key features of a G-quadruplex involved in transcriptional regulation.
Abstract
Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element located upstream of the major transcription start site. The KRAS nuclease-hypersensitive element (NHE) region contains a G-rich element (22RT; 5'-AGGGCGGTGTGGGAATAGGGAA-3') and encompasses a Myc-associated zinc finger-binding site that regulates KRAS transcription. The NEH region therefore has been proposed as a target for new drugs that control KRAS transcription, which requires detailed knowledge of the NHE structure. In this study, we report a high-resolution NMR structure of the G-rich element within the KRAS NHE. We found that the G-rich element forms a parallel structure with three G-quartets connected by a four-nucleotide loop and two short one-nucleotide double-chain reversal loops. In addition, a thymine bulge is found between G8 and G9. The loops of different lengths and the presence of a bulge between the G-quartets are structural elements that potentially can be targeted by small chemical ligands that would further stabilize the structure and interfere or block transcriptional regulators such as Myc-associated zinc finger from accessing their binding sites on the KRAS promoter. In conclusion, our work suggests a possible new route for the development of anticancer agents that could suppress KRAS expression.
NMRStructural Profiling of Transcriptional IntermediatesReveals Riboswitch Regulation by Metastable RNA Conformations
NMRStructural Profiling of Transcriptional IntermediatesReveals Riboswitch Regulation by Metastable RNA Conformations
Christina Helmling, Anna Wacker, Michael T. Wolfinger, Ivo L. Hofacker, Martin Hengesbach, Boris Fu?rtig and Harald Schwalbe
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/jacs.6b10429/20170210/images/medium/ja-2016-104296_0007.gif
Journal of the American Chemical Society
DOI: 10.1021/jacs.6b10429
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/wOFSRQbkFqs
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[NMR paper] High-resolution NMR reveals secondary structure and folding of amino Acid transporter from outer chloroplast membrane.
High-resolution NMR reveals secondary structure and folding of amino Acid transporter from outer chloroplast membrane.
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PLoS One. 2013;8(10):e78116
Authors: Zook JD, Molugu TR, Jacobsen NE, Lin G, Soll J, Cherry BR, Brown MF, Fromme P
Abstract
Solving high-resolution structures for membrane proteins continues to be a daunting challenge in the structural biology community. In this study we report our...
High dimensional and high resolution pulse sequences for backbone resonance assignment of intrinsically disordered proteins
High dimensional and high resolution pulse sequences for backbone resonance assignment of intrinsically disordered proteins
Abstract Four novel 5D (HACA(N)CONH, HNCOCACB, (HACA)CON(CA)CONH, (H)NCO(NCA)CONH), and one 6D ((H)NCO(N)CACONH) NMR pulse sequences are proposed. The new experiments employ non-uniform sampling that enables achieving high resolution in indirectly detected dimensions. The experiments facilitate resonance assignment of intrinsically disordered proteins. The novel pulse sequences were successfully tested using δ subunit (20 kDa) of Bacillus subtilis RNA polymerase...
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[NMR paper] Influence of chemical shift tolerances on NMR structure calculations using ARIA proto
Influence of chemical shift tolerances on NMR structure calculations using ARIA protocols for assigning NOE data.
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J Biomol NMR. 2005 Jan;31(1):21-34
Authors: Fossi M, Linge J, Labudde D, Leitner D, Nilges M, Oschkinat H
Large-scale protein structure determination by NMR via automatic assignment of NOESY spectra requires the adjustment of several parameters for optimal performance. Among those are the chemical shift...
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[NMR paper] NMR structure reveals intramolecular regulation mechanism for pheromone binding and r
NMR structure reveals intramolecular regulation mechanism for pheromone binding and release.
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Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14374-9
Authors: Horst R, Damberger F, Luginbühl P, Güntert P, Peng G, Nikonova L, Leal WS, Wüthrich K
Odorants are transmitted by small hydrophobic molecules that cross the aqueous sensillar lymph surrounding the dendrites of the olfactory neurons to stimulate the olfactory receptors. In insects, the...
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[NMR paper] The three-dimensional high resolution structure of human interferon alpha-2a determin
The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution.
J Mol Biol. 1997 Dec 12;274(4):661-75
Authors: Klaus W, Gsell B, Labhardt AM, Wipf B, Senn H
The solution structure of recombinant human interferon...