Abstract
Owing to its great threat to human health and environment, Pb2+ 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 Pb2+-detection sensors, but the underlying mechanisms remain elusive. Here, we report three Pb2+-complexed structures of the thrombin binding aptamer (TBA). These high-resolution crystal structures showed that TBA forms intramolecular G-quadruplex and Pb2+ is bound by the two G-tetrads in the center. Compared to K+-stabilized G-quadruplexes, the coordinating distance between Pb2+ 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 Pb2+-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 Pb2+-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.
Highlights
Owing to its great threat to human health and environment, Pb2+ pollution has been recognized as a major public problem by the World Health Organization (WHO)
Owing to its great threat to human health, Pb poisoning has been recognized as one major public problem
Exampled by PS2.M14, PW17, T30695 and the thrombin binding aptamer (TBA), many Pb2+-binding DNA aptamers are rich in guanines
Summary
Owing to its great threat to human health and environment, Pb2+ pollution has been recognized as a major public problem by the World Health Organization (WHO). No crystals were obtained for PS2.M, PW17 or T30695, we solved two TBA-Pb2+ complex structures with high-resolution in both A-form and B-form (Table 1). The A-form structure belongs to the tetragonal space group P41212; it contains two TBA-Pb2+ complexes per asymmetric unit (Fig. 1B).
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