Umami polypeptide detection system targeting the human T1R1 receptor and its taste-presenting mechanism

Chuanxi Zhang; Yulu Miao; Yinghui Feng; Jiawei Wang; Zhuoli Tian; Juan Dong; Bei Gao; Lujia Zhang

doi:10.1016/j.biomaterials.2022.121660

Umami polypeptide detection system targeting the human T1R1 receptor and its taste-presenting mechanism

Biomaterials. 2022 Aug:287:121660. doi: 10.1016/j.biomaterials.2022.121660. Epub 2022 Jun 28.

Authors

Chuanxi Zhang¹, Yulu Miao², Yinghui Feng², Jiawei Wang³, Zhuoli Tian², Juan Dong⁴, Bei Gao⁵, Lujia Zhang⁶

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China; School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China; Department of Micro/Nano Electronics, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai , 200240, China.
² Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
³ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China; School of Health Science and Engineering, University of Shanghai for Science and Tecchnology, Shanghai, 200093, China.
⁴ School of Food Science and Technology, Shihezi University, Shihezi, 832000, China.
⁵ School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China. Electronic address: gaobei@ecust.edu.cn.
⁶ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, 200062, China. Electronic address: ljzhang@chem.ecnu.edu.cn.

PMID: 35792387
DOI: 10.1016/j.biomaterials.2022.121660

Abstract

Umami is one of five basic tastes, the elucidation of its mechanism by the study of the interaction between umami polypeptides and hT1R1 umami receptors is of great significance. However, research on umami peptides targeting human T1R1 receptors is lacking, and the molecular mechanism remains elusive. Here, we successfully established a system to detect umami peptides targeting human T1R1 receptors by fluorescence spectroscopy, Surface Plasmon Resonance (SPR) and computational simulation. The sensory evaluation, calculated Kd value, and experimental affinity results between the four selected umami peptides (GRVSNCAA, KGDEESLA, KGGGGP, and TGDPEK) and glutamate were tested using this system, and all matched well. The maximum Ka value of GRVSNCAA was 479.55 M^-1, and the minimum affinity of TGDPEK was 2.67 M^-1. Computational simulations showed that the different peptide binding sites in the hT1R1 binding pocket occupied due to conformational changes are important factors for different taste thresholds, and that peptide hydrophobicity plays an important role in regulating affinity. Thus, our study enables rapid screening of high-intensity umami peptides and the development of T1R1 receptor-based umami detection sensors.

Keywords: Detection system; Interaction; Umami petides; hT1R1 receptor.