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bioRxiv · 10.64898/2026.06.26.734732

Recognition Mechanism of Serotonin by a G-Quadruplex-Duplex Hybrid Aptamer

Xu, G.·Wang, C.·Kang, M.·Chen, J.·Wei, J.·Zhao, Q.·Liu, M.·Li, C.
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Abstract

Serotonin is a key neurotransmitter, and aptamer-based tools using the 44-nt Apt44 have been successfully developed for its in vitro and in vivo detection. Nevertheless, the structural basis of recognition by this aptamer remains unclear. Here we report high-resolution NMR structures of Apt38, a 6-nt truncated variant in the third loop of Apt44, in free and serotonin-bound states. Both structures reveal a two-layered antiparallel chair-type G-quadruplex core with three edgewise loops and a terminal duplex, forming a G-quadruplex-duplex hybrid structure. Serotonin binds at the G-quadruplex-duplex junction, stabilized by stacking, electrostatic attraction, hydrogen bonding, and hydrophobic contacts. Apt38 is preorganized for binding, whereas the longer third loop of Apt44 introduces conformational dynamics into the G-quadruplex scaffold, which enables a pronounced binding-triggered conformational switch in PBS buffer, explaining its sensing mechanism. Our work reveals the recognition and sensing mechanism of the serotonin aptamer and provides a framework for aptamer design in serotonin biosensing.

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Xu, G., Wang, C., Kang, M., Chen, J., Wei, J., Zhao, Q., Liu, M., Li, C.. 2026-07-01. Recognition Mechanism of Serotonin by a G-Quadruplex-Duplex Hybrid Aptamer. https://doi.org/10.64898/2026.06.26.734732

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