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Structure-guided development of Pb2+-binding DNA aptamers.

Authors :
Liu, Hehua
Gao, Yanqing
Mathivanan, Johnsi
Shen, Fusheng
Chen, Xi
Li, Yangyang
Shao, Zhiwei
Zhang, Yixi
Shao, Qiyuan
Sheng, Jia
Gan, Jianhua
Source :
Scientific Reports; 1/10/2022, Vol. 12 Issue 1, p1-11, 11p
Publication Year :
2022

Abstract

Owing to its great threat to human health and environment, Pb<superscript>2+</superscript> pollution has been recognized as a major public problem by the World Health Organization (WHO). Many DNA aptamers have been utilized in the development of Pb<superscript>2+</superscript>-detection sensors, but the underlying mechanisms remain elusive. Here, we report three Pb<superscript>2+</superscript>-complexed structures of the thrombin binding aptamer (TBA). These high-resolution crystal structures showed that TBA forms intramolecular G-quadruplex and Pb<superscript>2+</superscript> is bound by the two G-tetrads in the center. Compared to K<superscript>+</superscript>-stabilized G-quadruplexes, the coordinating distance between Pb<superscript>2+</superscript> and the G-tetrads are much shorter. The T3T4 and T12T13 linkers play important roles in dimerization and crystallization of TBA, but they are changeable for Pb<superscript>2+</superscript>-binding. In combination with mutagenesis and CD spectra, the G8C mutant structure unraveled that the T7G8T9 linker of TBA is also variable. In addition to expansion of the Pb<superscript>2+</superscript>-binding aptamer sequences, our study also set up one great example for quick and rational development of other aptamers with similar or optimized binding activity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20452322
Volume :
12
Issue :
1
Database :
Complementary Index
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
154610983
Full Text :
https://doi.org/10.1038/s41598-021-04243-2