Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex
G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU (or DHX36) - a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadru...
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sg-ntu-dr.10356-1505412023-02-28T19:47:08Z Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex Heddi, Brahim Cheong, Vee Vee Schmitt, Emmanuelle Mechulam, Yves Phan, Anh Tuân School of Physical and Mathematical Sciences NTU Institute of Structural Biology Science::Biological sciences G-quadruplex X-ray Crystallography G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU (or DHX36) - a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadruplexes efficiently. We report a X-ray co-crystal structure at 1.5 Å resolution of an N-terminal fragment of RHAU bound to an exposed tetrad of a parallel-stranded G-quadruplex. The RHAU peptide folds into an L-shaped α-helix, and binds to a G-quadruplex through π-stacking and electrostatic interactions. X-ray crystal structure of our complex identified key amino acid residues important for G-quadruplex-peptide binding interaction at the 3'-end G•G•G•G tetrad. Together with previous solution and crystal structures of RHAU bound to the 5'-end G•G•G•G and G•G•A•T tetrads, our crystal structure highlights the occurrence of a robust G-quadruplex recognition motif within RHAU that can adapt to different accessible tetrads. Ministry of Education (MOE) Accepted version This work was supported by Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2018-T2-2-029). No competing financial interests have been declared. We thank Julien Lescar and Abbas El Sahili for collecting the diffraction data. 2021-05-25T03:19:09Z 2021-05-25T03:19:09Z 2019 Journal Article Heddi, B., Cheong, V. V., Schmitt, E., Mechulam, Y. & Phan, A. T. (2019). Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex. Journal of Structural Biology, 209(1), 107399-. https://dx.doi.org/10.1016/j.jsb.2019.10.001 1047-8477 https://hdl.handle.net/10356/150541 10.1016/j.jsb.2019.10.001 31586599 2-s2.0-85075419239 1 209 107399 en MOE2018-T2-2-029 Journal of Structural Biology © 2019 Elsevier Inc. All rights reserved. This paper was published in Journal of Structural Biology and is made available with permission of Elsevier Inc. application/pdf |
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Science::Biological sciences G-quadruplex X-ray Crystallography Heddi, Brahim Cheong, Vee Vee Schmitt, Emmanuelle Mechulam, Yves Phan, Anh Tuân Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex |
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G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU (or DHX36) - a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadruplexes efficiently. We report a X-ray co-crystal structure at 1.5 Å resolution of an N-terminal fragment of RHAU bound to an exposed tetrad of a parallel-stranded G-quadruplex. The RHAU peptide folds into an L-shaped α-helix, and binds to a G-quadruplex through π-stacking and electrostatic interactions. X-ray crystal structure of our complex identified key amino acid residues important for G-quadruplex-peptide binding interaction at the 3'-end G•G•G•G tetrad. Together with previous solution and crystal structures of RHAU bound to the 5'-end G•G•G•G and G•G•A•T tetrads, our crystal structure highlights the occurrence of a robust G-quadruplex recognition motif within RHAU that can adapt to different accessible tetrads. |
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School of Physical and Mathematical Sciences |
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School of Physical and Mathematical Sciences Heddi, Brahim Cheong, Vee Vee Schmitt, Emmanuelle Mechulam, Yves Phan, Anh Tuân |
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Article |
author |
Heddi, Brahim Cheong, Vee Vee Schmitt, Emmanuelle Mechulam, Yves Phan, Anh Tuân |
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Heddi, Brahim |
title |
Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex |
title_short |
Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex |
title_full |
Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex |
title_fullStr |
Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex |
title_full_unstemmed |
Recognition of different base tetrads by RHAU (DHX36) : X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex |
title_sort |
recognition of different base tetrads by rhau (dhx36) : x-ray crystal structure of the g4 recognition motif bound to the 3'-end tetrad of a dna g-quadruplex |
publishDate |
2021 |
url |
https://hdl.handle.net/10356/150541 |
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1759855199992676352 |