Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1
G-quadruplexes are four-stranded nucleic acid structures involved in multiple cellular pathways including DNA replication and telomere maintenance. Such structures are formed by G-rich DNA sequences typified by telomeric DNA repeats. Whilst there is evidence for proteins that bind and regulate G-qua...
Saved in:
Main Authors: | , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2020
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/145061 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-145061 |
---|---|
record_format |
dspace |
spelling |
sg-ntu-dr.10356-1450612023-02-28T16:57:53Z Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1 Traczyk, Anna Liew, Chong Wai Gill, David James Rhodes, Daniela School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) School of Chemical and Biomedical Engineering NTU Institute of Structural Biology Science::Biological sciences DNA Guanine Quadruplex G-quadruplexes are four-stranded nucleic acid structures involved in multiple cellular pathways including DNA replication and telomere maintenance. Such structures are formed by G-rich DNA sequences typified by telomeric DNA repeats. Whilst there is evidence for proteins that bind and regulate G-quadruplex formation, the molecular basis for this remains poorly understood. The budding yeast telomeric protein Rap1, originally identified as a transcriptional regulator functioning by recognizing double-stranded DNA binding sites, was one of the first proteins to be discovered to also bind and promote G-quadruplex formation in vitro. Here, we present the 2.4 Å resolution crystal structure of the Rap1 DNA-binding domain in complex with a G-quadruplex. Our structure not only provides a detailed insight into the structural basis for G-quadruplex recognition by a protein, but also gives a mechanistic understanding of how the same DNA-binding domain adapts to specifically recognize different DNA structures. The key observation is the DNA-recognition helix functions in a bimodal manner: In double-stranded DNA recognition one helix face makes electrostatic interactions with the major groove of DNA, whereas in G-quadruplex recognition a different helix face is used to make primarily hydrophobic interactions with the planar face of a G-tetrad. Ministry of Education (MOE) Published version Singapore Ministry of Education Academic Research Fund (AcRF) Tier 3 [MOE2012-T3-1-001]. Funding for open access charge: Singapore Ministry of Education Academic Research. 2020-12-09T09:24:04Z 2020-12-09T09:24:04Z 2020 Journal Article Traczyk, A., Liew, C. W., Gill, D. J., Rhodes, D. (2020). Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1. Nucleic Acids Research, 48(8), 4562–4571. doi:10.1093/nar/gkaa171 0305-1048 https://hdl.handle.net/10356/145061 10.1093/nar/gkaa171 32187364 8 48 4562 4571 en MOE2012-T3-1-001 Nucleic Acids Research © 2020 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License(http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original workis properly cited. For commercial re-use, please contact journals.permissions@oup.com application/pdf |
institution |
Nanyang Technological University |
building |
NTU Library |
continent |
Asia |
country |
Singapore Singapore |
content_provider |
NTU Library |
collection |
DR-NTU |
language |
English |
topic |
Science::Biological sciences DNA Guanine Quadruplex |
spellingShingle |
Science::Biological sciences DNA Guanine Quadruplex Traczyk, Anna Liew, Chong Wai Gill, David James Rhodes, Daniela Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1 |
description |
G-quadruplexes are four-stranded nucleic acid structures involved in multiple cellular pathways including DNA replication and telomere maintenance. Such structures are formed by G-rich DNA sequences typified by telomeric DNA repeats. Whilst there is evidence for proteins that bind and regulate G-quadruplex formation, the molecular basis for this remains poorly understood. The budding yeast telomeric protein Rap1, originally identified as a transcriptional regulator functioning by recognizing double-stranded DNA binding sites, was one of the first proteins to be discovered to also bind and promote G-quadruplex formation in vitro. Here, we present the 2.4 Å resolution crystal structure of the Rap1 DNA-binding domain in complex with a G-quadruplex. Our structure not only provides a detailed insight into the structural basis for G-quadruplex recognition by a protein, but also gives a mechanistic understanding of how the same DNA-binding domain adapts to specifically recognize different DNA structures. The key observation is the DNA-recognition helix functions in a bimodal manner: In double-stranded DNA recognition one helix face makes electrostatic interactions with the major groove of DNA, whereas in G-quadruplex recognition a different helix face is used to make primarily hydrophobic interactions with the planar face of a G-tetrad. |
author2 |
School of Biological Sciences |
author_facet |
School of Biological Sciences Traczyk, Anna Liew, Chong Wai Gill, David James Rhodes, Daniela |
format |
Article |
author |
Traczyk, Anna Liew, Chong Wai Gill, David James Rhodes, Daniela |
author_sort |
Traczyk, Anna |
title |
Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1 |
title_short |
Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1 |
title_full |
Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1 |
title_fullStr |
Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1 |
title_full_unstemmed |
Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1 |
title_sort |
structural basis of g-quadruplex dna recognition by the yeast telomeric protein rap1 |
publishDate |
2020 |
url |
https://hdl.handle.net/10356/145061 |
_version_ |
1759857073285234688 |