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Cell Biochemistry and Biophysics

, Volume 77, Issue 3, pp 227–243 | Cite as

Introducing a New Model of Sweet Taste Receptor, a Class C G-protein Coupled Receptor (C GPCR)

  • Elaheh Kashani-Amin
  • Amirhossein Sakhteman
  • Bagher Larijani
  • Azadeh Ebrahim-HabibiEmail author
Original Paper
  • 274 Downloads

Abstract

The structure of sweet taste receptor (STR), a heterodimer of class C G-protein coupled receptors comprising T1R2 and T1R3 molecules, is still undetermined. In this study, a new enhanced model of the receptor is introduced based on the most recent templates. The improvement, stability, and reliability of the model are discussed in details. Each domain of the protein, i.e., VFTM, CR, and TMD, were separately constructed by hybrid-model construction methods and then assembled to build whole monomers. Overall, 680 ns molecular dynamics simulation was performed for the individual domains, the whole monomers and the heterodimer form of the VFTM orthosteric binding site. The latter’s structure obtained from 200 ns simulation was docked with aspartame; among various binding sites suggested by FTMAP server, the experimentally suggested binding domain in T1R2 was retrieved. Local three-dimensional structures and helices spans were evaluated and showed acceptable accordance with the template structures and secondary structure predictions. Individual domains and whole monomer structures were found stable and reliable to be used. In conclusion, several validations have shown reliability of the new and enhanced models for further molecular modeling studies on structure and function of STR and C GPCRs.

Keywords

Sweet taste receptor T1R2 T1R3 C GPCR Homology modeling 

Abbreviations

STR

Human sweet taste receptor

C GPCR

Class C of G-protein coupled receptors

7TM

Seven transmembrane α-helices

VFTM

Venus flytrap domain or module

CR

Cysteine-rich domain

TMD

Transmembrane domain

mGluR1

Metabotropic glutamate receptor subtype 1

MD

Molecular dynamics

N-model

The new model introduced in the current study

R-model

The most recent model presented

I-model

Model represented by I-TASSER or GPCR-I-TASSER

SS

Secondary structure

ns

Nanoseconds

PME

Particle mesh Ewald

RMSD

Root mean square deviation

CA

Carbon-alpha

SD

Standard deviation

SDR

Standard deviation ratio

Notes

Acknowledgements

We thank the Non-Communicable Diseases Research Center of Endocrinology and Metabolism Population Sciences Institute and Dr. Latifeh Navidpour for allocating computational resources to help this project.

Funding

This research has been supported by the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences.

Author Contributions

This report contains part of the results obtained from E.K.-A. Ph.D. thesis project who has done model constructions, validations, calculations and analyses, and written the manuscript text draft. A.E-H. was supervisor of the thesis, developed the initial idea and supervised the research project from data gathering to critical paper review. A.S. was advisor of the thesis and has done technical supervision of the model construction, validation, and analyses and critical paper review. B.L. was advisor of the thesis and has contributed in the idea developing and supervising project progress as an endocrine and metabolism research study. All authors have reviewed the final script and commented if necessary.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12013_2019_872_MOESM1_ESM.pdf (619 kb)
Supplementary Material

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Authors and Affiliations

  1. 1.Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
  2. 2.Department of Medicinal Chemistry, School of PharmacyShiraz University of Medical SciencesShirazIran
  3. 3.Medicinal Chemistry and Natural Products Research CenterShiraz University of Medical SciencesShirazIran
  4. 4.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran

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