1.Introduction

         Sun jinpeng，Professor

1 Winner of The National Science Fund for Distinguished Young Scholars (2018)

New Cornerstone investigator (2023)

  

  Dr. Sun Jinpeng and the team has been engaged in the research of membrane receptor G protein coupled receptor (GPCR) for a long time. We have systematically studied the mechanism of GPCR sensing microenvironment and regulating physiological function, analyzed the molecular mechanism of GPCR sensing itch, smell, force and carbon-carbon double bond, discovered the recognition of steroid hormone membrane receptor subfamily, and realized the identification of many important GPCR endogenous ligands. A series of working models of GPCR preference are also proposed, including the flute model of GPCR signal transduction and the theory of proline terminal separation, which lays a theoretical foundation for the development of GPCR preference ligands. As the corresponding author, Dr. Sun Jinpeng has published more than 80 articles in Nature (×7), Science (×1, cover article), Cell (×2, 1 cover articles), Nature Metabolism (×1), Cell Metabolism (×1), Nat Chem Biol (×3), Cell Research (×2), PNAS (×6), Nat Commun (×7) and so on.

Education

1998 B.Sc. University of Science and Technology of China (USTC).
2001 M.S. University of Science and Technology of China (USTC).
2007 PhD. Albert Einstein College of Medicine, Bronx, New York. (USA)
2007-2011 Postdoctor, Research Associate. Advisor: Robert Lefkowitz, James B. Duke Professor of Medicine and Biochemistry and Investigator, Howard Hughes Medical Institute (2012 Nobel Prize)

2.Research of Focus

Our laboratory focused on G protein coupled receptors, in particular, the ligand identification, physiological functions and molecular mechanism of biased signaling of GPCR.

The main research content are shown as followed:

Our first main research aspect is the identification of endogenous ligand of GPCRs. We have identified the receptor subfamily to sense the steroid hormones. For instance, membrane receptor GPR97 is able to sense glucocorticoid to mediate its rapid actions, the progesterone and 17-hydroxyprogesterone membrane receptor are GPR126. We also identified DHEA, DHEAS and DOC are endogenous ligands of GPR64 etc (Nature, 2021a, Nat Chem Biol 2022, PNAS 2022b). By collaboration with Prof. Wei Kong, we found Nidogen as the agonist of LGR4 and the COMP is an endogenous allosteric ligand of AT1R (Circulation Research 2022, Cell Research 2021). By collaboration with Prof. Xiao Yu, we identified that Olfr109 could recognized denatured insulin and insulin fragment to control the insulin quality (Cell Metabolism 2022).

Our second main research aspect is dissecting the molecular mechanism underlying sensation of force, ordor and itch by GPCRs. We have elucidate the mechanism of receptors' perception of itch, olfactory and force (Nature 2021b, 2022a, 2022b, 2023).

Our third main research aspect is working mechanism of GPCR. For arrestin mediated biased signaling, we have proposed the “flute model” and “poly proline region docking theory” etc. to explain the arrestin mediated GPCR functions (Nature communications, 2015, 2021, 2022; PNAS 2021, Molecular Pharmacology, 2017; Recommended by Faculty 1000, Nature Chemical Biology 2018). We proposed that the 10 distinct phosphorylation interacting sites along the N-terminal of arrestin is the “phospho-code” reader of the arrestin, which recognized the information passed by GPCR, then translated to more then 1000 distinct functions. Our discovery can partially explain how limited effector proteins (16 G protein subtype and 4 arrestin subtype) can translate sophisticated information dictated from more than 800 GPCR to numerous cellular functions. We identified a new mechanism in activation of ion channel by GPCRs. A prototype thinking is that the ion channels are activated by GPCRs through either direct G protein interaction or second messengers downstream of G protein activation. We identified that arrestin can mediated AT1R/TRPC3 or M3R/TRPC3 coupling by forming a complex of AT1R/β-arrestin-1/PLCγ/TRPC3 or M3R//β-arrestin-1/TRPC3 (Nature communications, 2017, Nature communications, 2018). We also identified that orphan receptor GPR64 forms complex with β-arrestin-1 and CFTR at apical membrane of efferent ductules to regulate the salt/water metabolism (eLife 2018, Faculty 1000 recommendation). These work provided new mechanisms for GPCR activated ion channel, which may be relevant to many physiological or pathological processes.

Our fourth main research aspect is ligand coding mechanisms and structural aided drug discovery of GPCR. We have decoded the mechanisms underlying recognition of fish oil (unsaturated fatty acids) and other lipids by GPCRs (Science 2023, Science Advance 2021, PNAS 2023, Nature Metabolism 2023), recognition of amine containing hormones by GPCRs (Cell 2021), bile acids or its derivatives by GPCRs (Nature 2020).

3.Lab members

Dr. Tie Lu Associate Professor Email: bmp1985@163.com

Dr. Li Shuo Lecturer Email: lishuo@bjmu.edu.cn

Dr. JIA Yingli Research Associate Email: yingli0430@126.com

4.Selected Publications

1. Shang P, Rong NK, Jiang JJ, Cheng J, Zhang MH, Kang DW, Qi L, Guo LL, Yang GM, Liu Q, Zhou ZZ, Li XB, Zhu KK, Meng QB, Han X, Yan WQ, Kong YL, Yang LJ, Wang XH, Lei DP, Feng X, Liu XY, Yu X, Wang Y#, Li Q#, Shao ZH#, Yang F#, Sun JP#. Structural and signaling mechanism of TAAR1 enabled preferential agonist design. Cell. 2023 Nov 9:S0092-8674(23)01131-5. (IF 64.5) corresponding author

2. Xu Z, Guo L, Yu JJ,Shen SY,Wu C, Zhang WF, Zhao C, Deng Y, Tian XW, Feng YY, Hou HL, Su LT, Wang HS, Guo S, Wang HL, Wang KX, Chen PP, Zhao J, Zhang XY, Yong XH, Cheng L, Liu LX, Yang SY, Yang F, Wang XH, Yu X#, Xu YF#, Sun JP#, Yan W#, Shao ZH#. Molecular mechanisms of diverse ligand recognition and G proteins. Nature. 2023 Nov 7. doi: 10.1038/s41586-023-06804-z.（IF 64.8）corresponding author

3.Guo L, Cheng J, Lian S, Liu Q, Lu Y, Zheng Y, Zhu K, Zhang M, Kong Y, Zhang C, Rong N, Zhuang Y, Fang G, Jiang J, Zhang T, Han X, Liu Z, Xia M, Liu S, Zhang L, Liberles SD, Yu X, Xu Y#, Yang F#, Li Q#, Sun JP#. Structural basis of amine odorant perception by a mammal olfactory receptor. Nature. （IF 64.8） 2023 Jun;618(7963):193-200. corresponding author

4. Mao C, Xiao P, Tao XN, Qin J, He QT, Zhang C, Guo SC, Du YQ, Chen LN, Shen DD, Yang ZS, Zhang HQ, Huang SM, He YH, Cheng J, Zhong YN, Shang P, Chen J, Zhang DL, Wang QL, Liu MX, Li GY, Guo Y, Xu HE, Wang C, Zhang C, Feng S#, Yu X#, Zhang Y#, Sun JP#. Unsaturated bond recognition leads to biased signal in a fatty acid receptor. Science. （IF 56.9） 2023 Apr 7;380(6640):eadd6220. corresponding author

5.Ping YQ, Xiao P, Yang F, Zhao RJ, Guo SC, Yan X, Wu X, Zhao FH, Zhou FL, Xi YT, Yin WH, He FD, Zhang DL, Zhu ZL, Jiang Y, Torsten Schöneberg, Ines Liebscher#, Xu H. Eric#, Sun JP#. Structural basis for the tethered peptide activation of adhesion GPCRs. Nature. （IF 64.8）. 2022 Apr;604(7907):763-770. corresponding author

6. Xiao P, Guo S, Wen X, He QT, Lin H, Huang SM, Gou L, Zhang C, Yang Z, Zhong YN, Yang CC, Li Y, Gong Z, Tao XN, Yang ZS, Lu Y, Li SL, He JY, Wang C, Zhang L#, Kong L#, Sun JP#, Yu X#. Tethered peptide activation mechanism of the adhesion GPCRs ADGRG2 and ADGRG4. Nature. （IF 64.8） 2022 Apr;604(7907):771-778. corresponding author

7. Ping YQ, Mao C, Xiao P, Zhao RJ, Jiang Y, Yang Z, An WT, Shen DD, Yang F, Zhang H, Qu C, Shen Q, Tian C, Li ZJ, Li S, Wang GY, Tao X, Wen X, Zhong YN, Yang J, Yi F, Yu X, Xu HE#, Zhang Y#, Sun JP#. Structures of the glucocorticoid-bound adhesion receptor GPR97-Go complex. Nature. （IF 64.8） 2021 Jan;589(7843):620-626. corresponding author (Get Faculty 1000 recommendation）

8. Yang F, Guo L, Li Y, Wang G, Wang J, Zhang C, Fang GX, Chen X, Liu L, Yan X, Liu Q, Qu C, Xu Y, Xiao P, Zhu Z, Li Z, Zhou J, Yu X, Gao N#, Sun JP#. Structure, function and pharmacology of human itch receptor complexes. Nature. （IF 64.8） 2021 Dec;600(7887):164-169. corresponding author

9. Xiao P, Yan W, Gou L, Zhong YN, Kong L, Wu C, Wen X, Yuan Y, Cao S, Qu C, Yang X, Yang CC, Xia A, Hu Z, Zhang Q, He YH, Zhang DL, Zhang C, Hou GH, Liu H, Zhu L, Fu P, Yang S, Rosenbaum DM, Sun JP#, Du Y#, Zhang L#, Yu X#, Shao Z#. Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes. Cell. （IF 64.5） 2021 Feb 18;184(4):943-956.e18. corresponding author

（Cover article）

10.Yang F, Mao C, Guo L, Lin J, Ming Q, Xiao P, Wu X, Shen Q, Guo S, Shen DD, Lu R, Zhang L, Huang S, Ping Y, Zhang C, Ma C, Zhang K, Liang X, Shen Y, Nan F, Yi F, Luca VC, Zhou J, Jiang C, Sun JP#, Xie X#, Yu X#, Zhang Y#. Structural basis of GPBAR activation and bile acid recognition. Nature. （IF 64.8） 2020 Nov;587(7834):499-504. corresponding author

5.Contact information
SUN Jinpeng
Professor, Department of Physiology and Pathophysiology, Peking University
Address (office):38 Xueyuan road, Haidian, Beijing, 100083; China
Phone (office): 086-01082805639
Email: sunjinpeng@bjmu.edu.cn or sunjinpengsdu@126.com