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Nucleic Acids Res. 2020 Mar 18. pii: gkaa171. doi: 10.1093/nar/gkaa171. [Epub ahead of print]

Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1.

Author information

1
School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, Singapore.
2
NTU Institute of Structural Biology, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore.
3
Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive, Singapore 636921, Singapore.
4
School of Chemical and Biomedical Engineering, Nanyang Technological University Singapore, 62 Nanyang Drive, Singapore 637459, Singapore.

Abstract

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.

PMID:
32187364
DOI:
10.1093/nar/gkaa171

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