Histamine-modulated Wettability Switching in G-protein-coupled Receptor Inspired Nanochannel for Potential Drug Screening and Biosensing

Overview

Journal Nat Commun

Specialty Biology

Date 2025 Feb 20

PMID 39979281

Authors

Qi Zhao

Xu-Qin Ran

Zhu-Ying Yan

Hai-Long Qian

Xiu-Ping Yan

Affiliations

Soon will be listed here.

Abstract

Histamine receptor, one typical G-protein-coupled receptor (GPCR), can be activated by histamine and form the most important drug targets involved in allergy and reflux diseases. Here, we report an artificial model to mimic the wettability-induced activation of natural GPCRs via histamine-modulated enhancement of wettability in a bionic nanochannel. The artificial receptor is constructed by introducing key recognition factors in nature, L-lysine modified fluorescein isothiocyanate (L-lysine-FITC), into a conical nanochannel. The conductance of the L-lysine-FITC-modified nanochannel increases with the histamine-induced wettability enhancement due to the various interactions between histamine and L-lysine-FITC molecules including hydrogen bonding and π-π interactions, as well as the proton transfer reaction. This study represents a crucial step towards the design of artificial GPCRs with wettability-induced activation and provides an opportunity to construct artificial models of GPCRs in a non-lipid environment. The developed artificial receptor has great potential application in medicinal chemistry, biosensors, and healthcare systems.

References

Xia R, Wang N, Xu Z, Lu Y, Song J, Zhang A . Cryo-EM structure of the human histamine H receptor/G complex. Nat Commun. 2021; 12(1):2086. PMC: 8027608. DOI: 10.1038/s41467-021-22427-2. View

Fried J, Swett J, Paulose Nadappuram B, Mol J, Edel J, Ivanov A . solid-state nanopore fabrication. Chem Soc Rev. 2021; 50(8):4974-4992. DOI: 10.1039/d0cs00924e. View

Xin W, Fu J, Qian Y, Fu L, Kong X, Ben T . Biomimetic KcsA channels with ultra-selective K transport for monovalent ion sieving. Nat Commun. 2022; 13(1):1701. PMC: 8971412. DOI: 10.1038/s41467-022-29382-6. View

Massari N, Nicoud M, Medina V . Histamine receptors and cancer pharmacology: an update. Br J Pharmacol. 2018; 177(3):516-538. PMC: 7012953. DOI: 10.1111/bph.14535. View

Schwartz J, Pollard H, Quach T . Histamine as a neurotransmitter in mammalian brain: neurochemical evidence. J Neurochem. 1980; 35(1):26-33. DOI: 10.1111/j.1471-4159.1980.tb12485.x. View

Maintz L, Novak N . Histamine and histamine intolerance. Am J Clin Nutr. 2007; 85(5):1185-96. DOI: 10.1093/ajcn/85.5.1185. View

Sun Z, Han C, Song M, Wen L, Tian D, Li H . Fabrication of cysteine-responsive biomimetic single nanochannels by a thiol-yne reaction strategy and their application for sensing in urine samples. Adv Mater. 2013; 26(3):455-60. DOI: 10.1002/adma.201303158. View

Watkins R, DAVIDSON I . Action of histamine on phasic and tonic components of vascular smooth muscle contraction. Experientia. 1980; 36(5):582-4. DOI: 10.1007/BF01965815. View

Quan J, Zhu F, Dhinakaran M, Yang Y, Johnson R, Li H . A Visible-Light-Regulated Chloride Transport Channel Inspired by Rhodopsin. Angew Chem Int Ed Engl. 2020; 60(6):2892-2897. DOI: 10.1002/anie.202012984. View

10.

Sun Y, Zhang F, Quan J, Zhu F, Hong W, Ma J . A biomimetic chiral-driven ionic gate constructed by pillar[6]arene-based host-guest systems. Nat Commun. 2018; 9(1):2617. PMC: 6033921. DOI: 10.1038/s41467-018-05103-w. View

11.

Li P, Kong X, Xie G, Xiao K, Zhang Z, Wen L . Adenosine-Activated Nanochannels Inspired by G-Protein-Coupled Receptors. Small. 2016; 12(14):1854-8. DOI: 10.1002/smll.201503863. View

12.

Barocelli E, Ballabeni V . Histamine in the control of gastric acid secretion: a topic review. Pharmacol Res. 2003; 47(4):299-304. DOI: 10.1016/s1043-6618(03)00009-4. View

13.

Li P, Xie G, Liu P, Kong X, Song Y, Wen L . Light-Driven ATP Transmembrane Transport Controlled by DNA Nanomachines. J Am Chem Soc. 2018; 140(47):16048-16052. DOI: 10.1021/jacs.8b10527. View

14.

Xu Y, Sui X, Jiang J, Zhai J, Gao L . Smooth Muscle Cell-Mimetic CO-Regulated Ion Nanochannels. Adv Mater. 2016; 28(48):10780-10785. DOI: 10.1002/adma.201603478. View

15.

Yuan S, Filipek S, Palczewski K, Vogel H . Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway. Nat Commun. 2014; 5:4733. DOI: 10.1038/ncomms5733. View

16.

Lemmon M, Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2010; 141(7):1117-34. PMC: 2914105. DOI: 10.1016/j.cell.2010.06.011. View

17.

Jia R, Tian W, Bai H, Zhang J, Wang S, Zhang J . Amine-responsive cellulose-based ratiometric fluorescent materials for real-time and visual detection of shrimp and crab freshness. Nat Commun. 2019; 10(1):795. PMC: 6377604. DOI: 10.1038/s41467-019-08675-3. View

18.

Shang X, Xie G, Kong X, Zhang Z, Zhang Y, Tian W . An Artificial CO -Driven Ionic Gate Inspired by Olfactory Sensory Neurons in Mosquitoes. Adv Mater. 2016; 29(3). DOI: 10.1002/adma.201603884. View

19.

Hou X, Zhang H, Jiang L . Building bio-inspired artificial functional nanochannels: from symmetric to asymmetric modification. Angew Chem Int Ed Engl. 2012; 51(22):5296-307. DOI: 10.1002/anie.201104904. View

20.

Venkatakrishnan A, Deupi X, Lebon G, Tate C, Schertler G, Babu M . Molecular signatures of G-protein-coupled receptors. Nature. 2013; 494(7436):185-94. DOI: 10.1038/nature11896. View