Structural basis for sugar perception by Drosophila gustatory receptors

Author:

Ma Demin12ORCID,Hu Meiqin34ORCID,Yang Xiaotong34ORCID,Liu Qiang34ORCID,Ye Fan12ORCID,Cai Weijie34ORCID,Wang Yong5ORCID,Xu Ximing6ORCID,Chang Shenghai7ORCID,Wang Ruiying8ORCID,Yang Wei19ORCID,Ye Sheng10ORCID,Su Nannan11ORCID,Fan Minrui8ORCID,Xu Haoxing3412ORCID,Guo Jiangtao1291314ORCID

Affiliation:

1. Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.

2. Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China.

3. Department of Neurology and Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310058, China.

4. New Cornerstone Science Laboratory, Liangzhu Laboratory and School of Basic Medical Sciences, Zhejiang University, Hangzhou 311121, China.

5. College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.

6. Marine Biomedical Institute of Qingdao, School of Pharmacy and Medicine, Ocean University of China, Qingdao, Shandong 266100, China.

7. Center of Cryo-Electron Microscopy, Zhejiang University School of Medicine, Hangzhou 310058, China.

8. CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.

9. NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.

10. Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, School of Life Sciences, Tianjin University, Tianjin 300072, China.

11. International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China.

12. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.

13. State Key Laboratory of Plant Environmental Resilience, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.

14. Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.

Abstract

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.

Publisher

American Association for the Advancement of Science (AAAS)

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