Structural basis for parallel G-quadruplex recognition by an ankyrin protein

G-Quadruplex (G4) structures formed by guanine-rich DNA and RNA sequences are implicated in various biological processes. Understanding the mechanisms by which proteins recognize G4 structures is crucial for elucidating their functional roles. Here we present the X-ray crystal structure of an ankyri...

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Main Authors: Ngo, Khac Huy, Liew, Chong Wai, Heddi, Brahim, Phan, Anh Tuân
Other Authors: School of Physical and Mathematical Sciences
Format: Journal Article
Language:English
Published: 2024
Subjects:
Online Access:https://hdl.handle.net/10356/179281
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author Ngo, Khac Huy
Liew, Chong Wai
Heddi, Brahim
Phan, Anh Tuân
author2 School of Physical and Mathematical Sciences
author_facet School of Physical and Mathematical Sciences
Ngo, Khac Huy
Liew, Chong Wai
Heddi, Brahim
Phan, Anh Tuân
author_sort Ngo, Khac Huy
collection NTU
description G-Quadruplex (G4) structures formed by guanine-rich DNA and RNA sequences are implicated in various biological processes. Understanding the mechanisms by which proteins recognize G4 structures is crucial for elucidating their functional roles. Here we present the X-ray crystal structure of an ankyrin protein bound to a parallel G4 structure. Our findings reveal a new specific recognition mode in which a bundle of α-helices and loops of the ankyrin form a flat surface to stack on the G-tetrad core. The protein employs a combination of hydrogen bonds and hydrophobic contacts to interact with the G4, and electrostatic interaction is used to enhance the binding affinity. This binding mechanism provides valuable insights into understanding G4 recognition by proteins.
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spelling ntu-10356/1792812024-07-24T06:52:30Z Structural basis for parallel G-quadruplex recognition by an ankyrin protein Ngo, Khac Huy Liew, Chong Wai Heddi, Brahim Phan, Anh Tuân School of Physical and Mathematical Sciences NTU Institute of Structural Biology Chemistry G-Quadruplexes RNA sequences G-Quadruplex (G4) structures formed by guanine-rich DNA and RNA sequences are implicated in various biological processes. Understanding the mechanisms by which proteins recognize G4 structures is crucial for elucidating their functional roles. Here we present the X-ray crystal structure of an ankyrin protein bound to a parallel G4 structure. Our findings reveal a new specific recognition mode in which a bundle of α-helices and loops of the ankyrin form a flat surface to stack on the G-tetrad core. The protein employs a combination of hydrogen bonds and hydrophobic contacts to interact with the G4, and electrostatic interaction is used to enhance the binding affinity. This binding mechanism provides valuable insights into understanding G4 recognition by proteins. Nanyang Technological University This research was supported by grants from Nanyang Technological University to A.T.P. 2024-07-24T06:52:29Z 2024-07-24T06:52:29Z 2024 Journal Article Ngo, K. H., Liew, C. W., Heddi, B. & Phan, A. T. (2024). Structural basis for parallel G-quadruplex recognition by an ankyrin protein. Journal of the American Chemical Society, 146(20), 13709-13713. https://dx.doi.org/10.1021/jacs.4c01971 0002-7863 https://hdl.handle.net/10356/179281 10.1021/jacs.4c01971 38738955 2-s2.0-85193290971 20 146 13709 13713 en Journal of the American Chemical Society © 2024 American Chemical Society. All rights reserved.
spellingShingle Chemistry
G-Quadruplexes
RNA sequences
Ngo, Khac Huy
Liew, Chong Wai
Heddi, Brahim
Phan, Anh Tuân
Structural basis for parallel G-quadruplex recognition by an ankyrin protein
title Structural basis for parallel G-quadruplex recognition by an ankyrin protein
title_full Structural basis for parallel G-quadruplex recognition by an ankyrin protein
title_fullStr Structural basis for parallel G-quadruplex recognition by an ankyrin protein
title_full_unstemmed Structural basis for parallel G-quadruplex recognition by an ankyrin protein
title_short Structural basis for parallel G-quadruplex recognition by an ankyrin protein
title_sort structural basis for parallel g quadruplex recognition by an ankyrin protein
topic Chemistry
G-Quadruplexes
RNA sequences
url https://hdl.handle.net/10356/179281
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